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Epigenetics Podcast from Active Motif
Discover the stories behind the science.
Active Motif's Epigenetics Podcast is a lively discussion about the latest tips and techniques for epigenetics research. Podcast host Dr. Stefan Dillinger chats with experts from different fields within epigenetics about the latest research findings, the hottest epigenetics applications, and how to overcome the many challenges of ChIP and other epigenetic assays.
The Epigenetics of Human Sperm Cells (Sarah Kimmins)
In this episode of the Epigenetics Podcast, we caught up with Sarah Kimmins from Université de Montreal to talk about her work on the epigenetics of human sperm cells.
The focus of Sarah Kimmins and her lab is how sperm and offspring health is impacted by the father's environment. The core of this is the sperm epigenome, which has been implicated in complex diseases such as infertility, cancer, diabetes, schizophrenia and autism. The Kimmins lab is interested which players play a role in this and came across the Histone post-translational modification H3K4me3. In this interview we talk about how the father's life choices can impact offspring health, which can also be inherited transgenerationally and how this can be used to develop intervention strategies to improve child and adult health.
Transgenerational Inheritance and Evolution of Epimutations (Peter Sarkies)
In this episode of the Epigenetics Podcast, we caught up with Peter Sarkies from University of Oxford Biochemistry to talk about his work on Transgenerational Inheritance of Epimutations.
The team in the Sarkies lab focuses on investigating the connections between epigenetic gene regulation and evolution. The lab performs evolution experiments in the nematode C. elegans to determine if evolution can be influenced by epigenetic differences between individuals in a given population when no changes in the underlying DNA sequence are observed. A second area of interest of the team is evolution of piRNAs, which are present in metazoans but have been lost in nematodes during evolution.
Transcription Elongation Control by the Paf1 Complex (Karen Arndt)
In this episode of the Epigenetics Podcast, we caught up with Karen Arndt from the University of Pittsburgh to talk about her work on transcription elongation control by the Paf1 complex.
Karen Arndt and her lab investigate the process of transcriptional elongation and how RNA polymerase II overcomes obstacles like nucleosomes. One of the proteins that helps overcome those obstacles is the Paf1 complex. This complex associates with the transcribing polymerase and helps in modifying the chromatin template by ubiquitinating Histone H2B and methylating Histone H3.
Molecular Mechanisms of Chromatin Modifying Enzymes (Karim-Jean Armache)
In this episode of the Epigenetics Podcast, we caught up with Karim-Jean Armache from New York University - Grossman School of Medicine to talk about his work on the structural analysis of Polycomb Complex Proteins.
Karim-Jean Armache started his research career with the structural characterization of the 12-subunit RNA Polymerase II. After starting his own lab he used this knowledge in x-ray crystallography and electron microscopy to study how gene silencing complexes like the PRC complex act on chromatin and influence transcription. Further work in the Armache Lab focused on the Dot1, a histone H3K79 methyltransferase, and how it acts on chromatin, as well as how it is regulated by Histone-Histone crosstalk.
The Role of PHF13 in Chromatin and Transcription (Sarah Kinkley)
In this episode of the Epigenetics Podcast, we caught up with Sarah Kinkley from the Max Planck Institute of Molecular Genetics to talk about her work on PHF13 and its role in chromatin and transcription.
The Kinkley laboratory focuses mainly on unraveling the mechanism of action of the transcription factor PHF13 (PHC Finger Protein 13). PHF13 is a reader of the epigenetic mark H3K4 trimethylation which influences higher chromatin order, transcriptional regulation, and differentiation. The lab has shown that PHF13 plays a crucial role in phase separation and mitotic chromatin compaction.
Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis)
In this episode of the Epigenetics Podcast, we caught up with Akis Papantonis from the University Medical Center Göttingen to talk about his work on genome organisation mediated by RNA Polymerase II.
The research of the Papantonis Laboratory focuses on investigating how environmental signalling stimuli are integrated by chromatin to control homeostatic to deregulated functional transitions. In more detail, the team is interested in how dynamic higher-order regulatory networks are influenced by the underlying linear DNA fiber. The ultimate goal of the laboratory is to understand general rules governing transcriptional and chromatin homeostasis and finally, how those rules might affect development, ageing or malignancies.
The Role of Pioneer Factors Zelda and Grainyhead at the Maternal-to-Zygotic Transition (Melissa Harrison)
In this episode of the Epigenetics Podcast, we caught up with Melissa Harrison from the University of Wisconsin-Madison to talk about her work on the “Pioneer” Transcription Factors - Zelda and Grainyhead - and their role at the maternal-to-zygotic transition.
The Harrison lab studies how differentiation and development are driven by coordinated changes in gene expression. To do this, the targets of choice are the transcription factors Zelda and Grainyhead that bind to the genome at specific and crucial points in development and differentiation. These specialised transcription factors have the ability to bind to DNA in the context of nucleosomes which defines regulatory elements and leads to subsequent binding of additional classical transcription factors. These properties allow pioneer factors to act at the top of gene regulatory networks and control developmental transitions.
Epigenetics in Human Malaria Parasites (Elena Gómez-Diaz)
In this episode of the Epigenetics Podcast, we caught up with Elena Gomez-Diaz from the Institute of Parasitology and Biomedicine López-Neyra at the Spanish National Research Council. She shared with us her work on the Epigenetics in Human Malaria Parasites.
Elena Gómez-Díaz and her team are focusing on understanding how epigenetic processes are implicated in host-parasite interactions by regulating gene expression in the model of malaria. The team has started to investigate and uncover layers of chromatin regulation that control developmental transitions in Plasmodium falciparum, especially in the parts of the life cycle that take place in the mosquito. Furthermore, the lab has investigated epigenetic changes that are present in malaria-infected Anopheles mosquitos, this led to the identification of cis-regulatory elements and enhancer-promoter networks in response to infection.
Bioinformatic Analysis in Epigenetics Research (Nick Pervolarakis)
In this episode of the Epigenetics Podcast, we caught up with Nick Pervolarakis from Active Motif to talk about bioinformatic analysis in epigenetics research.
While many “bench scientists” are familiar with the workflows of ChIP-Seq, ATAC-Seq and CUT&Tag, and even the preparation and analysis of the libraries, the steps between sequencing and fully analyzed data is sometimes thought of as a mystery known only to bioinformatic experts. Most of us have some understanding that the raw data is usually in a file format called a FASTQ. But how do we get from FASTQ files to peaks on a genome browser? This Podcast Episode will provide a peek behind the curtain of the informatic analysis we perform at Active Motif, as part of our end-to-end epigenetic services.
Anchor-Based Bisulfite Sequencing (Ben Delatte)
In this episode of the Epigenetics Podcast, we caught up with Ben Delatte Research Scientist at Active Motif to talk about his work on Anchor Based Bisulfite Sequencing.
Whole Genome Bisulfite Sequencing (WGBS) is the current standard for DNA methylation profiling. However, this approach is costly as it requires sequencing coverage over the entire genome. Here we introduce Anchor-Based Bisulfite Sequencing (ABBS). ABBS captures accurate DNA methylation information in Escherichia coli and mammals, while requiring up to 10 times fewer sequencing reads than WGBS. ABBS interrogates the entire genome and is not restricted to the CpG islands assayed by methods like Reduced Representation Bisulfite Sequencing (RRBS). The ABBS protocol is simple and can be performed in a single day.
Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)
In this episode of the Epigenetics Podcast, we caught up with Susanne Mandrup from the University of Southern Denmark to talk about her work on the role of enhancer communities in adipocyte differentiation.
The Laboratory of Susanne Mandrup focuses on the effect of enhancers and enhancer communities on the differentiation of mesenchymal stem cell into adipocytes and osteoblasts. The team has shown that there is significant cross-talk between enhancers and that these form communities of highly interconnected enhancers. Inactive enhancers are then activated by association with these pre-existing enhancer networks to facilitate gene expression in adipocyte differentiation.
Transposable Elements in Gene Regulation and Evolution (Marco Trizzino)
In this episode of the Epigenetics Podcast, we caught up with Marco Trizzino from Thomas Jefferson University to talk about his work on transposable elements in gene regulation and evolution.
Marco Trizzino and his team focus on characterising transposable elements and how they affect gene regulation, evolution and ageing in primates. They could show that transposable elements that integrated into the genome turned into regulatory elements in the genome, like enhancers. They then contribute to regulation of processes like development or ageing, which could be among those factors that lead to increased brain development or longevity in great apes.
Hydroxymethylation Landscape in Immune Cells (Marcela Sjöberg)
In this episode of the Epigenetics Podcast, we caught up with Marcela Sjöberg from the University of Chile to talk about her work on the hydroxymethylation landscape in immune cells.
At the beginning of her career Marcela Sjöberg worked on Polycomb and how modifications placed by this complex modulate the binding of RNA Pol II. Later, her focus shifted to hydroxymethylated cytosine and how it is involved in the inheritance of Metastable Epialleles in mouse. More recently, the laboratory is interested in transcription factor binding motifs and how hydroxymethylation of those binding motifs modulates the binding and activity of the respective transcription factors.
Single Cell Epigenomics in Neuronal Development (Tim Petros)
In this episode of the Epigenetics Podcast, we caught up with Tim Petros from the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the NIH to talk about his work on Single Cell Epigenomics in Neuronal Development.
The Petros lab focuses on “interneurons”, their diversity and how environmental signals interact to generate this diversity. This subgroup of neurons comprise about 20% of neutrons in the brain, however, they are the primary source of inhibition. Furthermore, interneurons are critical components in modulating information flow throughout the nervous system. The Petros lab seeks to uncover the genetic programs that lead to the incredible diversity in interneurons, as well as how the local environment influences this process.
To lay a foundation for this and to provide a data-base for other researchers the Petros lab generated an epigenome atlas of neural progenitor cells of the mouse brain. This data includes scRNA-Seq, snATAC-Seq, CUT&Tag (H3K4me3, H3K27me3), CUT&RUN (H3K27ac), Hi-C and Capture-C. This data can be downloaded from the NIH website.
Oncohistones as Drivers of Pediatric Brain Tumors (Nada Jabado)
In this episode of the Epigenetics Podcast, we caught up with Nada Jabado from McGill University to talk about her work on oncohistones as drivers of Pediatric Brain Tumors.
Nada Jabado and her team were amongst the first to identify mutations in Histone 3.3 Tails which lead to differentially remodelled chromatin in pediatric glioblastoma. Mutations that occur include the Lysine at position 27 and the Glycine at position 34. If those residues are mutated it will influence the equilibrium of chromatin associated proteins like the Polycomb Repressive Complex (PRC) and hence domains of heterochromatin will be shifted. This, in turn, will lead to differential gene expression and development of developmental disorders or cancer.
Characterization of Epigenetic States in the Oligodendrocyte Lineage (Gonçalo Castelo-Branco)
In this episode of the Epigenetics Podcast, we caught up with Goncalo Castelo-Branco from the Karolinska Institute to talk about his work on the characterization of epigenetic states in the Oligodendrocyte Lineage.
The group from Gonçalo Castelo-Branco’s lab focuses on characterizing epigenetic states of oligodendrocytes, with the aim to understand their contribution to diseases like multiple sclerosis. To do this the group used single-cell RNA-Seq to identify sub-populations of oligodendrocytes. Furthermore, the team pioneered improvements in CUT&Tag and applied it to the single-cell space, as well as developing spatial CUT&Tag. More recently they used nanobodies in an optimised version of single cell CUT&Tag that allows simultaneous probing of three epigenomic modalities at single-cell resolution, using nanobody-Tn5 fusion proteins. The three modalities encompass chromatin accessibility as measured via ATAC-Seq and two histone post-transcriptional modifications.
Multiple challenges of ATAC-Seq, Points to Consider (Yuan Xue)
In this episode of the Epigenetics Podcast, we caught up with Active Motif’s own Yuan Xue to talk about some of the challenges of performing ATAC-Seq.
ATAC-Seq stands for Assay for Transposase-Accessible Chromatin with high-throughput sequencing and was initially described by Jason Buenrostro in 2013. The ATAC-Seq method relies on next-generation sequencing (NGS) library construction using the hyperactive transposase Tn5. NGS adapters are loaded onto the transposase, which allows simultaneous fragmentation of chromatin and integration of those adapters into open chromatin regions. ATAC-Seq is an attractive method to start your epigenetic journey. Whether you want to analyze the state of the chromatin in your sample or compare the chromatin state before and after a special treatment, ATAC-Seq allows you to investigate genome-wide chromatin changes and can offer guidelines about which epigenetic modification or transcription factor should be studied next in the follow-up experiments and which method should be used to study them.
In this Episode we go through the Protocol in detail and discuss potential challenges and points to pay attention to when starting your first ATAC-Seq experiment.
The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn)
In this episode of the Epigenetics Podcast, we caught up with John Rinn from the University of Colorado in Boulder to talk about his work on the role of lncRNAs in gene expression and nuclear organization.
The Rinn Lab pioneered the approach of screening the human genome for long noncoding RNAs (lncRNAs). More recently, the lab has shifted focus from measuring the number of lncRNAs to finding lncRNAs that have a distinct biological function in human health and disease. One example of such a lncRNA is FIRRE, which is present in all animals, however the sequence is not conserved, except for in primates. FIRRE contains many interesting features, such as repeat sequences and CTCF binding sites. In absence of FIRRE, defects in the immune system can be observed and also some brain defects may also be observed.
Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine)
In this episode of the Epigenetics Podcast, we caught up with Morgan Levine from Altos lab to talk about her work on Epigenetic Clocks and Biomarkers of Ageing.
The Levine Lab focuses on deciphering mechanisms that lead to epigenetic ageing, which can be measured by epigenetic clocks. Epigenetic clocks were first described in 2011 by Bocklandt et al.. Later-on, the Horvath and the Hannum clock were described by using a combination of CpGs to calculate biological/epigenetic age in contrast to chronological age.
The Levine Lab themselves worked on generating an advanced version of an Epigenetic clock, called "DNAm PhenoAge" that will now be used, and not only in human samples. The team now moves to mouse models and to cells in a dish and using those models to investigate the mechanisms behind epigenetic ageing.
Epigenetic and Metabolic Regulation of Early Development (Jan Żylicz)
In this episode of the Epigenetics Podcast, we caught up with Jan Żylicz from the Novo Nordisk Foundation Center for Stem Cell Medicine to talk about his work on epigenetic and metabolic regulation of early development.
The focus of the Żylicz Lab is studying early development and how this process is influenced by epigenetic factors. In more detail, the team focuses on the function of chromatin modifiers in this process. Primed pluripotent epiblasts in vivo show a distinct chromatin landscape that is characterized by high levels of histone H3 lysine 9 dimethylation (H3K9me2) and rearranged Polycomb-associated histone H3 lysine 27 trimethylation (H3K27me3) at thousands of genes along the genome. However, the function of only about 100 loci is impaired. The Żylicz Lab tries to understand this process behind and also the cause of this discrepancy.
Multiple challenges of CUT&Tag (Cassidee McDonough, Kyle Tanguay)
In this episode of the Epigenetics Podcast, we caught up with Active Motif scientists Casidee McDonough from Epigenetic Services and Kyle Tanguay from R&D to talk about technical details of the CUT&Tag protocol and current developments around this method in our R&D Team.
CUT&Tag, which is short for Cleavage Under Targets and Tagmentation, is a molecular biology method that is used to investigate interactions between proteins and DNA and to identify DNA binding sites for their protein of interest. Although CUT&Tag is similar in some ways to ChIP assays, the starting material for CUT&Tag is live, permeabilized cells or isolated cell nuclei, rather than cells or tissue that have been crosslinked with formaldehyde as is the case when performing ChIP. The CUT&Tag method is very sensitive and has been reported to work with as few as 60 cells for some histone modifications. The ability to work with such small numbers of cells is an advantage for researchers working on specific cell types, such as rare neuronal populations, pancreatic islets, or stem cells that are difficult to obtain in large numbers.
In this Episode we discuss the CUT&Tag workflow in detail, talk about the challenges and pitfalls, give guidelines on how to do a good CUT&Tag experiment and offer a glimpse into the future of CUT&Tag product development at Active Motif.
The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze)
In this episode of the Epigenetics Podcast, we caught up with Ian Maze from Ichan School of Medicine at Mount Sinai and a Howard Hughes Medical Institute (HHMI) Investigator to talk about his work on the role of histone dopaminylation and serotinylation in neuronal plasticity.
The Maze group focuses on understanding the complex interplay between chromatin regulatory mechanisms in brain and neuronal plasticity. The lab places an emphasis on psychiatric disorders associated with monoaminergic (e.g., serotonin, dopamine, etc.) dysfunction, such as major depressive disorder and drug addiction. In particular the Maze team has investigated cocaine addiction and its effect on chromatin by serotonylation and dopaminylation of Histone H3 Tails.
The Role of Blimp-1 in Immune-Cell Differentiation (Erna Magnúsdóttir)
In this episode of the Epigenetics Podcast, we caught up with Erna Magnúsdóttir from the University of Iceland to talk about her work on the role of Blimp-1 in immune-cell differentiation.
The Magnúsdóttir Lab is interested in how the mammalian genome is interpreted in a context dependent manner, leading to different cellular states, by using mouse primordial germ cells as well as mouse and human B-cells as model systems. More specifically, the team is interested in the Transcription Factor Blimp-1 and its effect on immune cell differentiation. Next to its function in immune cells, Blimp-1 also plays a role in Waldenström’s macroglobulinemia. The lab hopes to reveal the intricacies in disease progression and alteration in cellular states to increasingly aggressive tumor behavior.
Multimodal Characterization of Cellular Identity | CITE-Seq and Beyond (Peter Smibert, VP of 10X Genomics)
In this episode of the Epigenetics Podcast, we speak with Peter Smibert, Vice President of Biology at 10X Genomics to talk about an exciting new method in Multimodal Characterization of Cellular Identity using Barcoding.
During his time at the New York Genome Center, Peter Smibert was instrumental in the development of a new method called "Cellular Indexing of Transcriptomes and Epitopes by Sequencing" short CITE-Seq. This method enables the characterization of a cell's transcriptome, while at the same time, also allows the characterization of the cell's protein surface markers - at the single cell level. In CITE-Seq, sequencing adapters are coupled to antibodies that recognize surface proteins, which can then be detected by sequencing.
Further advancements of the CITE-Seq method led to the launch of BioLegend’s TOTAL-Seq and the integration of scATAC-Seq into the workflow. With the integration of scATAC-Seq in the CITE-Seq protocol, it is now possible to characterize single-cells along the path of the central dogma of biology, this is why the method called DOGMA-Seq.
The Effect of Mechanotransduction on Chromatin Structure and Transcription in Stem Cells (Sara Wickström)
In this episode of the Epigenetics Podcast, we caught up with Sara Wickström, Director at the Max Planck Institute for Molecular Biomedicine in Münster, to talk about her work on the effect of mechanotransduction on chromatin structure and transcription in stem cells.
Sara Wickström and her team focus on the stem cell niche and how that niche affects stem cell function. In order to study the native niche and to even be able to manipulate it, the Wickström Lab was able to develop a ex vivo culture system, allowing systematic identification of factors driving stem cell dynamics and plasticity.
Stem cells in the stem cell niche are exposed to external stimuli such as physical forces which control their growth, fate and self renewal. Recent work in the Wickström lab showed how mechanical signals influence transcriptional regulation, chromatin organization, and nuclear architecture and how this affects aging or lineage commitment. In this Episode we also discuss how chromatin can act as a sensor of mechanical signals taking advantage of the different physical properties of eu- and heterochromatin.
Single-Cell Technologies using Microfluidics (Ben Hindson, CSO of 10x Genomics)
In this episode of the Epigenetics Podcast, we caught up with Ben Hindson, Chief Scientific Officer at 10X Genomics, to talk about single-cell technologies using microfluidics.
Epigenetics has moved well past a simple understanding of a single epigenetic layer of control at genomic regions of interest, thanks to advances in many techniques and the application of “multiomics”. We can now analyze genome-wide histone modification patterns, transcription factor binding profiles, chromatin accessibility profiles, three-dimensional chromosomal conformation, and DNA methylation dynamics combined with transcriptomic analyses and associated analytical platforms.
Bulk Assays, like ATAC-Seq or ChIP, despite all their advantages, do not provide information about the chromatin states of individual subpopulations of cells within a sample. To identify chromatin features in heterogeneous populations, such as blood, pancreas, and brain, those analysis need to be performed at a single-cell level. 10X Genomics has been at the forefront of the movement into the single cell space and in this Episode we discuss this work with Ben Hindson, CSO of 10X genomics.
Epigenome-based Precision Medicine (Eleni Tomazou)
In this episode of the Epigenetics Podcast, we caught up with Eleni Tomazou from St. Anna Children's Cancer Research Institute in Vienna to talk about her work on Epigenome-based precision medicine.
The Tomazou lab studies Ewing sarcoma and the effects of Epigenetic factors on this disease. Ewing sarcoma is a type of cancer that affects bone and soft tissue of children and young adults, with a peak incidence at the age of 15. Ewing sarcoma is among the pediatric cancer types with the lowest survival rates and the development of novel therapies was obstructed by the limited understanding of the mechanisms behind the disease.
Work done in Eleni Tomazou's group identified an epigenetic signature of Ewing sarcoma which, ultimately, lead to the possibility to diagnose Ewing sarcoma from liquid biopsies. The team is now looking to find actionable targets like enhancers to develop therapies, finding biomarkers to enable disease monitoring, and to further characterize these tumors to decipher intra-tumor epigenetic heterogeneity and characterize the developmental stage of the cell of origin.
Epigenetics and Epitranscriptomics in Cancer (Manel Esteller)
In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer.
The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments.
Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm)
In this episode of the Epigenetics Podcast, we caught up with Yad Ghavi-Helm from the Institut de Génomique Functionnelle de Lyon to talk about her work on enhancer-promoter interactions during development.
The Laboratory of Yad Ghavi-Helm focuses on how developmental genes are regulated by enhancers. Their work shows that developmental genes are often regulated by more than one enhancer and that those enhancers can often be located many kilobases away on the linear chromosome. Furthermore, their research also indicates that the interactions between promoters and their respective enhancers are usually established before the expression of the target gene is switched on, and that those interactions are generally stable during embryogenesis. In addition, those stable interactions seem to coincide with paused RNA Pol II being located at those promoters before gene activation.
The Effect of Vitamin D on the Epigenome (Folami Ideraabdullah)
In this episode of the Epigenetics Podcast, we caught up with Folami Ideraabdullah from the University of North Carolina at Chapel Hill to talk about her work on the environmental modulation of the epigenome during development.
The lab of Folami Ideraabdullah focuses on studying how environmental factors modulate the epigenome. In particular the team investigates how Vitamin D levels influence epigenetic processes and, hence, the susceptibility for diseases like adipositas. Folami Ideraabdullah started with a genome-wide screen of DNA Methylation patterns that are observed after Vitamin D depletion. This work was then followed up by investigating the impact of Vitamin D depletion on mouse sperm DNA methylation.
H3K4me3, SET Proteins, Isw1, and their Role in Transcription (Jane Mellor)
In this episode of the Epigenetics Podcast, we caught up with Jane Mellor from the University of Oxford to talk about her work on H3K4me3, SET proteins, Isw1 and their role in transcription.
Since the beginning of the century, Jane Mellor and her team have focused on H3K4 trimethylation and the factors that influence this mark. They discovered that H3K4me3 is an almost universal mark of the first nucleosome in every transcribed unit and all organisms. She could subsequently, together with the Tony Kouzarides lab, identify SetD1, the enzyme that is responsible for writing this modification. Later on, the team characterized Isw1, a chromatin remodeler which “reads” H3K4me3. More recently the lab focuses on how the polymerase transcribes throughout the first nucleosomes of the transcribed region at the +2 nucleosome, with the help of Spt4.
The Role of DNA Methylation in Epilepsy (Katja Kobow)
In this episode of the Epigenetics Podcast, we caught up with Katja Kobow from the Universitätsklinikum Erlangen to talk about her work on the role of DNA methylation in Epilepsy.
Katja Kobow started studying the role of Epigenetics in Epilepsy by doing a genome wide Bisulfite-Sequencing screen that revealed a typical DNA methylation signature of epileptic patients versus healthy controls. After these initial results in human patient samples, she switched to an animal model to investigate this further. Now the focus of the Kobow Lab is to look for the same DNA methylation signature in blood samples, using this as a basis for the development of a potential prognostic marker for Epilepsy.
MacroH2A Function in Development and Disease (Emily Bernstein)
In this episode of the Epigenetics Podcast, we caught up with Emily Bernstein from Icahn School of Medicine at Mount Sinai to talk about her work on MacroH2A function and the role of Polycomb proteins in its epigenetic regulation, and how this affects stem cell development and disease.
The Bernstein Lab focuses on histone variants, in particular the H2A variant macroH2A. Chromatin architecture is influenced by the composition of the nucleosome and, hence, exchanging the core histones for histone variants can have a major impact on chromatin structure. MacroH2A variants are the most unique histone variants due to a 30kDa non-histone domain (macro domain) at their C-termini. This macro domain likely confers important functions to macroH2A variants, which have important regulatory roles in the cell. Among other things, the Bernstein Lab has shown that macroH2A is enriched at a critical set of Utx target genes whose expression is critical for the early stages of induced pluripotency, and that macroH2A plays a role as a barrier to tumorigenesis.
Spatio-Temporal Alterations in Chromosome Dynamics (Jane Skok)
In this episode of the Epigenetics Podcast, we caught up with Jane Skok from New York University School of Medicine to talk about her work on spatio-temporal alterations in chromosome dynamics.
Studies demonstrating that nuclear organization and long-range chromatin interactions play essential roles in gene regulation have been the focus of the Skok Lab, where the team has played a leading role. Their initial studies focused on lymphocyte development and the control of V(D)J recombination, a key part of generating the diverse repertoire of B-cell antibodies and T-cell receptors. The Skok Lab was among the first to demonstrate the possibility of chromatin forming dynamic loops which lead to the formation of reversible intra-locus loops in the immunoglobulin and T-cell receptor loci and to a profound impact on the ability of B and T cells to generate receptor diversity.
Chromatin Organization During Development and Disease (Marieke Oudelaar)
In this episode of the Epigenetics Podcast, we caught up with Marieke Oudelaar from the Max Planck Institute for Biophysical Chemistry to talk about her work on chromatin organization during development and disease.
Marieke Oudelaar and her team focus on on developing high-resolution Chromosome Conformation Capture (3C) based techniques, like low-input Capture-C, Tri-C, and Tiled-C. Those techniques are then used in combination with other genomic techniques, genetic perturbations, and computational approaches to investigate the 3D structure of chromatin in development and disease. The team focused on the interplay between genome organisation and regulation during mammalian differentiation, and how perturbations in these processes contribute to human disease, including cancer.
Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos)
In this episode of the Epigenetics Podcast, we caught up with Camila dos Santos from Cold Spring Harbor Laboratories to talk about her work on enhancers and chromatin remodeling in mammary gland development.
The lab of Camila dos Santos focuses on epigenetic regulation of normal and malignant mammary gland development. After puberty, the next significant phase in mammary gland development occurs in pregnancy, including changes in cellular function, and tissue reorganization. A different and as significant change in mammary glands occurs in the development breast cancer.
Camila dos Santos and her lab were recently able to show that the reaction of mammary glands to a second pregnancy is different than to a first one, which is accompanied by changes in the DNA methylome of the cells. Furthermore, the lab studies the connection of pregnancy-induced epigenetic changes of chromatin and the risk of cancer development.
The Role of SMCHD1 in Development and Disease (Marnie Blewitt)
In this episode of the Epigenetics Podcast, we caught up with Marnie Blewitt from the Walter and Eliza Hall Institute of Medical Research to talk about her work on the role of SMCHD1 in Development and Disease.
The Laboratory of Marnie Blewitt focuses finding inhibitors or activators for the epigenetic regulator SMCHD1. Marnie Blewitt identified and characterized this protein during her PhD and the findings were published in 2008 in Nature Genetics. Since then, she and her team were able to investigate the function of this protein further. By doing so, they showed the involvement of SMCHD1 in cancer and several other diseases. Currently the lab is screening for small molecules that can act as inhibitors or activators of SMCHD1 the former as potential treatments for facioscapulohumeral muscular dystrophy, the latter for Prader Willi and Schaaf-Yang syndromes, both of which have no current targeted treatments.
Single-Molecule Imaging of the Epigenome (Efrat Shema)
In this episode of the Epigenetics Podcast, we caught up with Efrat Shema from the Weizmann Institute of Science to talk about her work on Single Molecule Imaging of chromatin, and the analysis of nucleosomes circulating in plasma.
In ChIP-Seq experiments the peak you get as a read out represents an average over, most often, millions of cells. Furthermore, one often does not know if that peak represents one or more than one nucleosome. If you then want to study multiple marks at the same time, the question remains: do those modifications occur at the same time, in the same cell?
The Laboratory of Efrat Shema works on answering those questions by developing methods to study the modification patterns on single nucleosomes with single molecule imaging. With that it is possible to study single nucleosomes in a high throughout manner to identify the modifications they are decorated with. A subsequent sequencing step makes it possible to identify the genomic location of that nucleosome.
Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli)
In this episode of the Epigenetics Podcast, we caught up with Serena Sanulli from Stanford University to talk about her work on Heterochromatin Protein 1 (HP1), the structure of chromatin on the atomic-scale and the meso-scale, and phase separation.
The Laboratory of Serena Sanulli is interested in finding connections between changes that happen on the nucleosomal level and the resulting impact on chromatin conformation on the meso-scale. They combine methods like NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology and Genetics. This enables them to dissect how cells use the diverse biophysical properties of chromatin to regulate gene expression across length and time scales.
A second focus of the lab is HP1, which interacts with the nucleosome and changes its conformation, enabling the compaction of the genome into heterochromatin, effectively silencing genes in that region. A high concentration of HP1 leads to the phenomenon of phase separation in the nucleus, which the Sanulli lab is now investigating.
The Effects of Early Life Stress on Mammalian Development (Catherine J. Peña)
In this episode of the Epigenetics Podcast, we caught up with Catherine Jensen Peña from Princeton University to talk about her work on early life stress and its effects on behavior.
The Peña lab focuses on how early life experiences are encoded and maintained into adulthood, with a long-lasting impact on behavior. Recent work shows that child maltreatment and other forms of early life stress increase the lifetime risk of depression and other mood, anxiety, and drug disorders by 2-4 fold. The Peña lab uses genome wide approaches to investigate key brain regions with a two-hit stress model.
Using RNA-Seq, the Peña Lab has shown that depression-like gene expression patterns are programmed by early life stress, similar to observations in mice exhibiting depression-like behavior after adult stress and are visible even before behavioral changes. Furthermore, latent and unique transcriptional responses to adult stress among a subset of genes is programmed by early life stress. The role of chromatin modifications in regulating these processes are investigated using state of the art technologies like Mod-Spec or ATAC-Seq.
Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)
In this episode of the Epigenetics Podcast, we caught up with Ali Shilatifard from Northwestern University to talk about his work on targeting COMPASS to cure childhood leukemia.
The Shilatifard Lab studies childhood leukemia and how it can potentially be treated using epigenetic targets. The team focuses on is SET1/COMPASS, a histone H3 lysine4 methylase. Ali Shilatifard was able to purify and identify its activity, with results published in 2001 in PNAS. This protein complex is conserved from yeast to drosophila to humans.
Surprisingly, the Shilatifard Team could show that the catalytic activity of COMPASS is not necessary for viability of drosophila. Furthermore, they found that catalytic activity was not the decisive feature of the complex, but rather its role in the context of chromatin structure, in particular a protein domain that only spans 80 amino acids within the 4000 amino acid protein.
Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David)
In this episode of the Epigenetics Podcast, we caught up with Yael David from Memorial Sloan Kettering Cancer Center in New York to talk about her work on Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin.
The David lab studies on non-enzymatic covalent modifications of Histones, including Histone glycation and citrullination. These modifications recognize metabolites that are produced in the cell and aid as a sensor for chromatin to quickly adapt to cellular changes. These unique modifications do not have a so-called erasing enzyme, which makes them terminal, rendering these sites inaccessible for further modifications such as methylation or acetylation.
A second area of research in the David lab is Histone H1. The lab has developed a new method to purify Histone H1, superior to the commonly used method of acid extraction which leads to degradation of Histone H1. This purification method enabled the lab to purify and characterize the functional properties of all Histone H1 variants.
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro)
In this episode of the Epigenetics Podcast, we caught up with Jason Buenrostro from Harvard University to talk about his work on developing biological tools to measure chromatin dynamics in single-cells.
We hear the story of how in his early years in the lab, Jason took a risk and added an enzyme called Transposase to cells in culture. What he saw on an agarose gel astonished him. He was able to recreate a nucleosomal ladder similar to using MNase or DNase-Seq, without the tedious steps of optimization. In following years he optimized the method into what is known today as ATAC-Seq. In recent years he was also able to bring ATAC-Seq to the next level, developing single cell ATAC-Seq (scATAC-Seq), and combining it with RNA-Seq in a multi-omics approach.
In this Episode we discuss how Jason Buenrostro developed ATAC-Seq in William Greenleaf's lab, how a lack of equipment shaped the ATAC-Seq protocol, and how scATAC-Seq has enabled a whole different way of looking at biological samples.
Synthetic Chromatin Epigenetics (Karmella Haynes)
In this episode of the Epigenetics Podcast, we caught up with Dr. Karmella Haynes from Emory University to talk about her work on synthetic chromatin epigenetics, specifically on the design of synthetic chromatin sensor proteins. The first one of its kind, the Polycomb Transcription Factor (PcTF), senses H3K27me3 and recruits effector proteins to the sites of this modification. This sensor can be brought into cancer cells to activate hundreds of silenced genes. The lab hopes to characterize these effects genome wide and seeks to find a way to deliver those sensor into cancer cells, without affecting healthy cells.
In this Episode we discuss how Karmella Haynes got into the field of Epigenetics and the way she came to learn how important the right control experiments are. In the end we also discuss her activities to promote diversity and inclusion in science.
Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab)
In this episode of the Epigenetics Podcast, we caught up with Dr. Enrico Glaab from the University of Luxembourg to talk about his work on the development of integrative machine learning tools for neurodegenerative diseases. The work of Dr. Enrico Glaab focuses on neurodegenerative disorders like Parkinson’s and Alzheimer’s disease. In his group his team works on the development of software tools to analyze molecular, clinical and neuroimaging data for those diseases that can be used and applied easily by scientists and deliver publication ready figures. More recently, Enrico Glaab's group got interested in the influence of Epigenetics in Parkinson's and Alzheimer's disease.
Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
In our 50th episode of the Epigenetics Podcast, we caught up with Dr. Diane Dickel from Lawrence Berkeley National Laboratory to talk about her work on ultraconserved enhancers and enhancer redundancy. We discuss how Diane Dickel and her team try to identify and characterize enhancers at a genomic scale and use CRISPR/CAS9 to mutate enhancer sequences in order to understand sequence dependent functional relevance. In addition, we chat about what ultraconservation actually means, how enhancer redundancy works and how Diane Dickel dealt with a failed PhD project.
Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)
In this episode of the Epigenetics Podcast, we caught up with Dr. Sandra Hake from the Justus Liebig University in Giessen to talk about her work on variants of core histones and their role as modulators of chromatin structure and function. In addition to discussing her approach to the characterization and identification of novel histone variants like H3.3, H3.X and H3.Y, we talk about what it's like to work in a small field like histone variants and what is coming up next for the Hake lab.
DNA Methylation and Mammalian Development (Déborah Bourc'his)
In this episode of the Epigenetics Podcast, we caught up with Dr. Déborah Bourc'his from L'Institut Curie in Paris to talk about her work on the role of DNA methylation in mammalian development. We discuss how she has been involved in the characterization of two methyltransferase enzymes; DNMT3L, which is responsible for stimulating gDNA methylation activity in male and female germlines and DNMT3C, which has evolved as a defense against transposons in rodents.
Chromatin Analysis using Mass Spectrometry (Axel Imhof)
In this episode of the Epigenetics Podcast, we caught up with Dr. Axel Imhof from Ludwig Maximilian University of Munich to discuss his lab’s work on the identification of chromatin associated proteins using mass spectrometry (MS). We discuss what has changed in the field of MS over the years, how he takes advantage of collaborations, how metabolites influence chromatin, and how he is helping to bring epigenetic profiling via MS to the clinic.
Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff)
In this episode of the Epigenetics Podcast, we caught up with Dr. Steven Henikoff from the Fred Hutchinson Cancer Research Center in Seattle to talk about the novel methods his lab has developed for profiling the chromatin landscape. By making use of enzyme tethering, the Henikoff lab has offered alternatives to ChIP which require less cells and take less time.
Effects of DNA Methylation on Diabetes (Charlotte Ling)
In this episode of the Epigenetics Podcast, we caught up with Dr. Charlotte Ling from Lund University in Sweden, to talk about her work on the role of DNA methylation in diabetes. The Ling lab investigates how differently methylated DNA is associated with diabetes risk, with its successful treatment, and how it can change with exercise. We discuss how Charlotte Ling ended up in the field of diabetes and how the results of her work are now used to develop blood-based biomarkers.
Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)
In this episode of the Epigenetics Podcast, we caught up with Dr. Monica Dus from the University of Michigan to talk about her work on nutriepigenetics and the effects of diet on behavior. The Dus lab is attempting to understand why animals are more likely to overeat if they consume foods rich in sugar, salt, and fat. We discuss how the sensory neurons of fruit flies can be reprogrammed with a high sugar diet, affecting both the taste and amount of they eat.
Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot)
In this episode of the Epigenetics Podcast, we caught up with Dr. Céline Vallot from L'Institut Curie in Paris to discuss her work on investigating the dynamics of epigenetic plasticity in cancer with single cell technologies. We discuss how she had her once-in-a-lifetime scientific eureka-moment, when, during her postdoc, she first saw XACT coating the whole X-Chromosome in humans and then how she pivoted when starting her own lab and focuses now on single-cell epigenomics in cancer.
Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell)
In this episode of the Epigenetics Podcast, we caught up with Dr. Margaret (“Peggy”) Goodell from Baylor College of Medicine in Houston, Texas to talk about her work on the epigenetic regulation of stem cell self-renewal and differentiation. We discuss how she developed a new method to isolate hematopoietic stem cells even though she wasn’t looking for it, how she discovered DNMT3A as an important factor in stem cell decision making, and how she entered and approached new fields of research along the path of her research career.
Genome-Wide Investigation of Epigenetic Marks and Nucleosome Positioning (Keji Zhao)
In this episode of the Epigenetics Podcast, we caught up with Dr. Keji Zhao from the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, MD, to talk about his work on the genome-wide investigation of epigenetic marks and nucleosome positioning. We also discuss the story behind how Dr. Keji Zhao was one of the pioneers of the chromatin immunoprecipitation technology, how he discovered the genomic locations of HATs and HDACs, and in the end he shares some tips and tricks on how to get the best results in ChIP-Seq assays.
The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier)
In this episode of the Epigenetics Podcast, we caught up with Dr. Sarah Diermeier from the University of Otago in New Zealand to talk about her work on the role of long non-coding RNAs in tumor growth and treatment. This episode also tells the stories behind how Dr. Sarah Diermeier ended up in New Zealand, how her childhood influenced her career path, the role of lncRNAs in cancer, and how she deals with being a young PI and a mother at the same time.
Unraveling Mechanisms of Chromosome Formation (Job Dekker)
In this episode of the Epigenetics Podcast, we caught up with Dr. Job Dekker from the University of Massachusetts Medical School to talk about his work on unraveling mechanisms of chromosome formation. We discuss the story behind the idea of the chromosome conformation capture method Dr. Dekker developed, how close he was to giving up on it, how the 3C methods evolved, the importance of data visualization, and we also touch on parts of his current work on dinoflagellates.
Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)
In this episode of the Epigenetics Podcast, we caught up with Dr. Danny Reinberg from the New York University School of Medicine to talk about his work on transcription and polycomb in inheritance and disease. This interview discusses the story behind how Dr. Danny Reinberg started his research career by identifying the essential RNA polymerase transcription factors, how he discovered and characterized the polycomb repressive complex 2 (PRC2), and what his research holds for the future.
The Epigenetics of COVID-19 (Sandra Atlante & Carlo Gaetano)
In this episode of the Epigenetics Podcast, we caught up with Dr. Sandra Atlante and Dr. Carlo Gaetano from the Istituti Clinici Scientifici Maugeri in Pavia, Italy, to talk about the roles epigenetic mechanisms play in COVID-19. In this episode we discuss how Dr. Atlante and Dr. Gaetano set up studies to investigate the epigenetic response to a SARS-CoV-2 infection, which epigenetic factors play a role in COVID-19 disease progression, and what we can expect from mutations of the virus in the future.
Epigenetic Reprogramming During Mammalian Development (Wolf Reik)
In this episode of the Epigenetics Podcast, we caught up with Dr. Wolf Reik, Director at the Babraham Institute in Cambridge, UK, to talk about his work on the role of epigenetic factors in cellular reprogramming. In this interview, we discuss the story behind how Dr. Wolf Reik almost discovered 5-hmC and how he later moved into developing single-cell methods like scRRBS and single-cell multi-omics approaches.
In Vivo Nucleosome Structure and Dynamics (Srinivas Ramachandran)
In this episode of the Epigenetics Podcast, we caught up with Dr. Srinivas Ramachandran, Assistant Professor at the University of Colorado, Anschutz Medical Campus, to talk about his work on in vivo nucleosome structure and dynamics. We discuss the story behind how Dr. Ramachandran found his way into chromatin research, what it was like to start a wet lab postdoc with a bioinformatics background, and what he is working on now to unravel nucleosomal structure and dynamics in his own lab.
Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)
In this episode of the Epigenetics Podcast, we caught up with Dr. Ken Zaret, Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania, to talk about his work on pioneer transcription factors and their influence on chromatin structure. We discuss the story behind how Dr. Zaret discovered pioneer transcription factors like FoxA, how these factors are influenced by the chromatin environment, and how they function.
The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)
In this episode of the Epigenetics Podcast, we caught up with Dr. Oded Rechavi, Professor at the University of Tel Aviv, to talk about his work on the role of small RNAs in transgenerational inheritance in C. elegans. In this interview, we cover how Dr. Rechavi chose C. elegans as a model organism, discuss his first major discoveries in the field of transgenerational effects of starvation, and what role small RNAs and other epigenetic factors play in this process.
Development of Site-Specific ChIP Technologies (Hodaka Fujii)
In this episode of the Epigenetics Podcast, we caught up with Dr. Hodaka Fujii, Professor of Biochemistry and Genome Biology at Hirosaki University Graduate School of Medicine and School of Medicine, to talk about his work on the development of locus-specific ChIP technologies. We also discuss the story behind how Dr. Fujii got into the field of epigenetics, how he developed iChIP, and how the method was improved over the years. Furthermore, we discuss the development of enChIP and how this method can be used as an alternative to Hi-C.
Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni)
Geneviève Almouzni is a leader in the field of epigenetics, and we are excited to welcome her as a guest on our Epigenetics Podcast. She discovered multiple histone chaperones and is working on unraveling the mechanisms responsible for nucleosome assembly as well as the links between chromatin structure at centromeres and cancer. In this interview, we sat down with Dr. Almouzni to learn about the stories behind her discoveries, what she’s focusing on now, how she got started in science (hint: it involves tadpoles!), and much more.
How the "Fragile Nucleosome" Science Community Came to Life (Christine Cucinotta, Melvin Noe Gonzalez)
In this episode of the Epigenetics Podcast, we caught up with Dr. Christine Cucinotta and Dr. Melvin Noe Gonzalez, members of the organizing committee for the independent "Fragile Nucleosome" scientific community, to talk about how they brought the #fragilenucleosome seminar series and Discord channel to life. In this interview, Christine and Melvin share the story of how the Fragile Nucleosome community got started, what has happened so far, and what the future plans are for the #fragilenucleosome.
Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy)
In this episode of the Epigenetics Podcast, we caught up with Professor Isabelle Mansuy, Ph.D. from the University of Zürich and the ETH Zürich, to talk about her work on epigenetic influences on memory formation and inheritance. Check out this interview to learn more about the challenges and obstacles that needed to be overcome to create a novel experimental approach to tackle the questions of whether and which epigenetic factors might influence transgenerational epigenetic inheritance.
Influence of Dynamic RNA Methylation on Gene Expression (Chuan He)
In this episode of the Epigenetics Podcast, we caught up with Dr. Chuan He, John T. Wilson Distinguished Service Professor at the University of Chicago, to talk about his work on the influence of dynamic RNA methylation on gene expression. In this interview, we discuss the story of how the He lab discovered the members of the family of proteins that read, write, and erase RNA modifications and the mechanisms of how those RNA modifications act in the field of epigenetics.
How to Publish in Nature: Lessons from the ENCODE Consortium (Michelle Trenkmann, Senior Editor at Nature)
In this episode of the Epigenetics Podcast, we caught up with Dr. Michelle Trenkmann, Senior Editor at Nature. We discussed her work as an editor at Nature and how she contributed to the ENCODE 3 publications, which are the results of the third phase of the ENCODE project. Dr. Trenkmann also talked about how to get your research published in Nature and what it’s like to review high profile scientific articles.
The Role of Non-Histone Proteins in Chromosome Structure and Function During Mitosis (Bill Earnshaw)
In this episode of the Epigenetics Podcast, we caught up with Professor Bill Earnshaw, Wellcome Trust Principal Research Fellow at the University of Edinburgh, to talk about his work on the role of non-histone proteins in chromosome structure and function during mitosis.
In this interview, we discuss the story on how centromeric proteins were first identified using sera from human scleroderma patients, how the chromosomal passenger complex was discovered, how condensin I and II work together in chromatin loop formation, and much more!
Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
In this episode of the Epigenetics Podcast, we caught up with Dr. Dirk Schübeler, Director of the Friedrich Miescher Institute in Basel, Switzerland, to talk about his work on the effects of DNA methylation on chromatin structure and transcription.
In this interview, we discuss the impact of DNA methylation on chromatin states, how CpG-binding factors influence those processes, and we also talk about his new role as Director of the Friedrich Miescher Institute.
CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)
In this episode of the Epigenetics Podcast, we caught up with Sir Adrian Bird, Buchanan Professor of Genetics at the University of Edinburgh, to talk about his work on CpG islands, DNA methylation, and the role of DNA methylation in human diseases.
In this interview, podcast host Stefan Dillinger and Adrian Bird discuss the discovery of the methyl-CpG-binding protein MeCP2, which is almost as abundant as histones in neurons. MeCP2 deficiencies in children can cause serious neurological diseases such as the autism spectrum disorder Rett Syndrome. Adrian Bird talks about how his research on MeCP2 may potentially lead to the discovery of a treatment for Rett Syndrome.
Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
In this episode of the Epigenetics Podcast, we caught up with Leonid Mirny, Ph.D., from Massachusetts Institute of Technology to talk about his work on biophysical modeling of the 3-D structure of chromatin.
In this interview, we chatted with Dr. Mirny about the details of Hi-C, the development of Micro-C and how it compares to Hi-C, and how biophysical modeling helps to unravel the mechanisms behind loop extrusion.
From Nucleosome Structure to Function (Karolin Luger)
In this episode of the Epigenetics Podcast, we caught up with Karolin Luger, Ph.D., from the University of Colorado in Boulder to talk about her work on solving the crystal structure of the nucleosome and on how histone chaperones like FACT act on chromatin.
In this interview, we discuss the efforts that went into solving the crystal structure of the nucleosome back in 1997, her work on histone chaperones, and her recent work on how FACT keeps nucleosomes intact after gene transcription.
Identification of Functional Elements in the Genome (Bing Ren)
In this episode of the Epigenetics Podcast, we caught up with Bing Ren, Ph.D., from the University of California, San Diego and the Ludwig Institute for Cancer Research to talk about his work on identifying functional elements in the genome and higher order genome structure.
Dr. Ren’s lab invented an approach for finding cis-elements that involves the identification of transcription factor binding sites and chromatin modification status genome-wide using chromatin immunoprecipitation-based methods. His group demonstrated that this is an effective approach for genome-wide mapping of cis-elements, and their approach has now been widely adopted in the field. Among many other distinctions, Bing Ren's group was also a major contributor to the ENCODE Project.
In this interview, we discuss the path Bing Ren has taken so far on scientific career, his role in the ENCODE Project and Roadmap Epigenome Consortia, and the discovery of topologically associating domains (TADs).
Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
In this episode of the Epigenetics Podcast, we caught up with Erez Lieberman Aiden, Ph.D. from Baylor College of Medicine and Rice University in Houston to talk about his work on developing Hi-C and investigating the three-dimensional structure of the genome. He was the first author on a publication in the journal Science titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" which was the paper that first introduced the Hi-C method in 2009 and he has continued studying the structure of the chromosome ever since.
Erez Liebermann Aiden is currently an Assistant Professor in both the Department of Genetics at the Baylor College of Medicine, where he directs the newly-established Center for Genome Architecture, and in the Department of Computer Science and Computational and Applied Mathematics at Rice University across the street.
In this interview, we discuss the road that Erez Liebermann Aiden went down to optimize the Hi-C protocol, the hurdles he had to overcome, and how Hi-C made it possible to probe the three-dimensional structure of the genome.
Chromatin Structure and Dynamics at Ribosomal RNA Genes (Tom Moss)
In this episode of the Epigenetics Podcast, we caught up with Professor Tom Moss from Université Laval in Québec City, Canada to talk about his work on the chromatin structure and dynamics at ribosomal RNA genes.
Dr. Tom Moss has been a member of the Department of Molecular Biology, Medical Biochemistry, and Pathology at the Laval University School of Medicine since he was recruited from the University of Portsmouth in the United Kingdom in 1986. Since then he focused on the ribosomal transcription factor Upstream Binding Factor (UBF) and how it regulates the chromatin structure at ribosomal RNA genes (rDNA).
UBF binds to the rDNA as a dimer where it leads to six in-phase bends and induces the formation of the ribosomal enhanceosome. This enhanceosome is required for the initial step in formation of an RNA polymerase I initiation complex, and therefore plays an important role in regulating the expression of ribosomal RNA genes.
In this interview, we discuss the function of UBF on the rDNA, how UBF impacts the chromatin landscape at rRNA genes, the role of DNA methylation in this process, and how UBF influences the structure of the nucleolus.
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
In this episode of the Epigenetics Podcast, we caught up with Dr. Andrew Pospisilik from the Van Andel Institute in Grand Rapids, Michigan to talk about his work on the epigenetic origins of heterogeneity and disease.
Dr. Andrew Pospisilik worked at the Max Planck Institute for Epigenetics in Freiburg for 8 years and in 2018 he joined the Van Andel Institute as the director of its Center for Epigenetics. At the Van Andel Institute his research focuses on diabetes, neurodegenerative diseases, cancer, and obesity. The goal of the Pospisilik Laboratory is to better understand epigenetic mechanisms of these diseases and the roles of epigenetics in disease susceptibility and heterogeneity.
These areas of medicine are among the most important public health challenges, with the latest estimates suggesting that they impact more than 1 billion people worldwide. Although these diverse conditions are all very different, they are now thought to be caused, at least partially, from alterations in the epigenetic mechanisms that regulate gene expression and metabolism.
This podcast interview covers recent work from the Pospisilik lab on the epigenetics of these complex diseases.
PIXUL: On the Leading Edge of Chromatin Shearing (Karol Bomsztyk and Tom Matula)
In this episode of the Epigenetics Podcast, we caught up with Karol Bomsztyk, M.D. and Tom Matula, Ph.D. from the University of Washington and Matchstick Technologies to talk about their work on DNA and chromatin sonication.
During his career, Karol's research has focused on improving ChIP protocols to make them faster, easier, and higher throughput. First, to make ChIP assays faster, Karol and his lab developed Fast ChIP. More recently, he adjusted this protocol to improve throughput and Matrix ChIP was born. Tom is an expert in the field of ultrasound physics and cavitation and the Director of the Center for Industrial and Medical Ultrasound at the University of Washington.
To further improve and speed up the 96-well Matrix ChIP protocol, Karol and Tom teamed up and co-founded Matchstick Technologies to develop a sonication device that would be able to processes each and every well of a 96-well microplate consistently and quickly. The result of this cooperation is the PIXUL Multi-Sample Sonicator that is now available for order from Active Motif.
PIXUL is an ultrasound-based sample preparation platform that was designed completely from the ground up to provide researchers with an easy-to-use tool that is simple to set up, simple to use, and generates consistent results day in and day out. No other sample preparation platform out there can match the power and convenience of PIXUL.
PIXUL was conceived by an epigenetics researcher and designed and built by ultrasound engineers to take the guesswork out of sample preparation. With PIXUL, sample preparation is no longer an art form, but instead a simple and predictable part of experiments that works every single time.
This interview goes into the mechanism behind sonication-based shearing of DNA and chromatin and highlights how PIXUL is different from existing sonication instruments.
Influence of Histone Variants on Chromatin Structure and Metabolism (Marcus Buschbeck)
In this episode of the Epigenetics Podcast, we sat down with Marcus Buschbeck, Group Leader at the Josep Carreras Leukaemia Research Institute in Barcelona, to talk about his work on the histone variant macroH2A, its role in metabolism, and how it contributes to the regulation of chromatin structure.
Histone variants equip chromatin with unique properties and show a specific genomic distribution. The histone variant macroH2A is unique in having a tripartite structure consisting of a N-terminal histone-fold, an intrinsically unstructured linker domain, and a C-terminal macro domain. Recent discoveries show that macroH2A proteins have a major role in nuclear organization, which has the potential to explain how these proteins can act as tumor suppressors, promoters of differentiation, and barriers to somatic cell reprogramming.
We discuss these topics, the mission of the Josep Carreras Leukaemia Research Institute, and much more in this episode.
Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)
In this episode of the Epigenetics Podcast, we sat down with Dr. Shelley Berger, Director of the Epigenetics Institute and Daniel S. Och Professor of Cell and Developmental Biology at the University of Pennsylvania School of Medicine, and Keynote Speaker at the EMBO | EMBL Symposium: Metabolism Meets Epigenetics, to talk about her work on epigenetic mechanisms of aging and longevity. We also discussed how cytoplasmic chromatin fragments are involved in these processes, how alcohol has an effect on histone PTMs in the brain, and how ants became her favorite model organism.
Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead)
In this episode of the Epigenetics Podcast our guest Dr. Lucy Stead, Head of Glioma Genomics at the University of Leeds, discusses her recent work on intratumor heterogeneity in glioblastoma brain tumors. Her research involves a true multidisciplinary approach, including computational genomics, in silico modeling, and functional genomics. She uses this experimental strategy to test whether treatment-resistant cancer cells emerge in recurrent tumors and characterizes them in clinically relevant ways in multiple patients.
And this is just a glimpse of the conversation. Listen to the podcast episode to learn more about this fascinating topic and potential new ways to treat brain cancer.
The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)
Joe Fernandez, the founder of Active Motif, has played a significant role in the evolution of the biotechnology industry. He’s seen where the industry has been, and he has a good idea where it’s going.
Prior to founding Active Motif in 1999, Joe was a co-founder of Invitrogen where he helped revolutionize molecular cloning with the TOPO TA kit. Joe’s passion for disrupting established workflows by making them easier and more efficient didn’t stop there. With Active Motif, he launched the first ever ChIP kit in 2003, and the company now offers the most complete portfolio of ChIP kits for different workflows and sample types, the highest quality ChIP-validated antibodies, and the most comprehensive and most cited end-to-end Epigenetic Services.
In this interview, we sat down with Joe to learn how he got started in science, what he’s currently excited about, and what he thinks will be the next big thing in epigenetics research.
Check out our blog post to learn more.
The Interchromatin Network Model (Ana Pombo)
There are many levels of control that contribute to regulating the levels of gene expression. One major mechanism of gene regulation involves organization of the genome within the nucleus. In this episode of the Epigenetics Podcast, our guest Professor Ana Pombo from the Max-Delbrück-Center in Berlin provides insight into her work on the interplay between gene regulation and genome architecture.
Dr. Pombo and her team use different state-of-the-art methods in their research, including cryo-sectioning, to unravel this regulatory network. In 2006, they proposed the "Interchromatin Network Model" of chromosome organization which postulates that chromosome folding is driven by contacts between different genomic regions and chromatin and nuclear landmarks, such as the nuclear lamina. They also used polymer physics modeling to study those mechanisms, which lead to the development of the "Strings and Binders Switch" model of chromatin organization.
Listen to the podcast episode to learn more about this fascinating topic.
Dosage Compensation in Drosophila (Asifa Akhtar)
For many organisms, from fruit flies to humans, sex is determined by the number of X chromosomes. Females often have two copies of the X and males have one, creating an imbalance in the number of X chromosome genes present in each sex. Different organisms have evolved different strategies for how to cope with this imbalance. For example, in humans, one of the two X chromosomes in every female cell is randomly inactivated, leaving both males and females with one active X chromosome each. However, in Drosophila, the balance is achieved by males overexpressing the genes on their single X chromosome two-fold to bring up the levels of gene expression to match expression from the two X chromosomes in females. Essentially the same end result is achieved in both humans and Drosophila, balanced levels of X chromosome transcription in both males and females, but using two extremely different mechanisms.
In this episode, our guest Dr. Asifa Akhtar, Senior Group Leader and Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany, discussed her lab's recent work on dosage compensation in Drosophila melanogaster. Dr. Akhtar talked about how the MSL complex, and the histone acetyltransferase MOF in particular, contributes to the regulation of the dosage compensation process. Furthermore, she also talked about some potential functions of the conserved MSL proteins in humans and how they are similar to and different from their fruit fly counterparts.
Check out our blog post to learn more.
Spatial Organization of the Human Genome (Wendy Bickmore)
In recent years it has become more and more evident that genome organization the nucleus plays a pivotal role in the regulation of gene expression. In this episode of our podcast we spoke with Professor Wendy Bickmore, Director of the MRC Human Genetics Unit at the University of Edinburgh, about her work on the spatial organization of the human genome. Professor Bickmore and her team use visual methods like fluorescence in situ hybridization (FISH) to study the organization of human and mouse chromosomes and investigate how organization of the genome contributes to transcriptional regulation. Dr. Bickmore's research group also studies how this organization changes during aging, development, and disease.
Check out our blog post to learn more.
Heterochromatin and Phase Separation (Gary Karpen)
Heterochromatin plays a pivotal role in organizing our genome in the nucleus and is probably most well known for marking inactive genomic regions. In this podcast episode our guest Gary Karpen from UC Berkeley sits down with us to talk about the regulation of this heterochromatin and how DNA repair mechanisms function in this densely packed nuclear compartment. We also discuss how phase separation might be an important part of the way that heterochromatin domains are formed.
Check out our blog post to learn more.
Diabetes and Epigenetics (Jean-Sébastien Annicotte)
Type 2 Diabetes (T2D) is a chronic metabolic disease that is caused by the failure of beta-cells in the pancreas and insulin resistance in peripheral tissue, and is characterized by high glucose levels in the blood. 382 million people suffer from diabetes worldwide, which makes up >8% of the global population.
Due to this high proportion of people affected, it is of high interest to find a cure for this disease and tremendous efforts have been made on deciphering epigenetic regulations that control metabolic tissue function.
For several years, the research team led by Dr. Jean-Sebastien Annicotte have dissected the molecular links between insulin producing cells, insulin target tissues, and T2D/obesity development. Their research has specifically been focused on the role of cell cycle regulators and their transcriptional co-regulators in the control of metabolic homeostasis, T2D and obesity.
In this podcast episode, we caught up with Dr. Jean-Sebastien Annicotte to discuss his views on type 2 diabetes and the roles of epigenetic mechanisms in regulating this disease.
Check out our blog post to learn more.
Epigenetics and X-Inactivation (Edith Heard)
In this episode of our Epigenetics Podcast, we sat down with Professor Edith Heard, the Director General of the European Molecular Biology Laboratory (EMBL), to talk about the challenges and goals of her new position as DG of the EMBL and her research on X-inactivation and dosage compensation.
Chromatin Organization (Susan Gasser)
In this episode of our Epigenetics Podcast, we caught up with Professor Susan Gasser, director of the Friedrich Miescher Institute in Basel, to talk about her research on heterochromatin, its localization in the nucleus and factors that are involved in the anchoring genomic regions at the nuclear periphery.
Epigenomics (Henk Stunnenberg)
In this episode of our Epigenetics Podcast, we chatted with Professor Henk Stunnenberg, head of the Department of Molecular Biology at the Radboud University in Nijmegen, to discuss his scientific work which led him to epigenetics research. Topics include his establishment of the BLUEPRINT and Human Cell Atlas consortia, a European collaborative database of at least 100 reference epigenomes of blood cells from healthy donors and their malignant counterparts, and his feelings about his recent knighthood.
Aging and Epigenetics (Peter Tessarz)
In this episode of our Epigenetics Podcast, we were joined by Dr. Peter Tessarz from the Max Planck Institute for Biology of Ageing in Cologne, and discussed the factors that influence the aging process in humans, how epigenetics comes into play, and how Peter's research can lead to a longer and healthier life.
Cancer and Epigenetics (David Jones)
In this episode of our Epigenetics Podcast, we visited Dr. David Jones at the DKFZ in Heidelberg to talk about the implications of epigenetics in cancer. We also talked about David's contributions to the field of pediatric brain tumors and the role of large consortia in doing science today and in the future.
The Nucleosome: From Atoms to Genomes (Ada and Don Olins)
In this episode of our Epigenetics Podcast we sat down with Ada and Don Olins at the EMBO meeting on "The Nucleosome: From Atoms to Genomes" to talk about their outstanding scientific journey together as a married couple and their perspectives on the future of the chromatin field.
Multiple Challenges in ChIP (Adam Blattler)
In this first episode of the Active Motif Epigenetics Podcast we chatted with Dr. Adam Blattler from the R&D team at Active Motif and discussed the multiple challenges of ChIP, the critical points of the ChIP protocol, as well as possible pitfalls.
Chromatin immunoprecipitation has become a very powerful method to study protein-DNA interactions, identify the binding profiles of DNA binding proteins, and determine whether specific proteins are associated with specific genomic regions. However, the workflow is complicated and involves many steps, so extensive experience and optimization are often required to achieve the best results.
Check out our Guide to Generating the Best ChIP Data on our blog for more details.