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p300 in Epigenetics and Disease
p300 (also known as EP300, or E1A binding protein p300) is a multifunctional transcriptional coactivator and histone acetyltransferase (HAT) that plays a pivotal role in gene regulation, chromatin remodeling, and cell signaling. It acetylates all four core histones, thereby loosening chromatin structure and facilitating transcriptional activation. The domain architecture of p300 includes several regions that enable interactions with a wide range of transcription factors, such as the bromodomain, nuclear receptor interaction domain (RID), CREB and MYB interaction domain (KIX), TAZ1 and TAZ2 cysteine/histidine-rich regions, and the interferon response binding domain (IBiD). Notably, p300 functions in both normal and disease contexts and has been implicated in various cancers, where it can act as either a tumor suppressor or an oncogene, depending on the cellular environment.
| Protein / Family | Epigenetic Function | Disease Association | Key Publications | Key Products |
|---|---|---|---|---|
| BRD4 | Chromatin-binding protein, Epigenetic reader that binds acetylated histones, recruits transcription machinery (p300) | Cancer (especially NUT carcinoma), inflammation, fibrosis | Umphred-Wilson et al., Nat Commun. 2025 Fan et al., Nat Commun. 2025 Zhang et al., Cell Rep. 2024 Cameron et al., Sci Adv. 2023 |
|
| CBP (CREBBP) | Co-activator protein, Histone acetyltransferase (HAT), Binds to phosphorylated CREB (at Ser133), acts as a scaffold and chromatin modifier | Rubinstein-Taybi syndrome (mutations in CBP/CREBBP), Cancer, Intellectual disability | Chen et al., J Neuropathol Exp Neurol. 2025 Liu et al., bioRxiv 2025 |
Antibodies Proteins |
| CREB (cAMP Response Element-Binding Protein) | Transcription factor, cAMP response, CREB phosphorylation and p300 recruitment | Cancer (glioblastoma, leukemia), Neurodegenerative diseases, Depression | Alva et al., Toxicol Lett. 2024 Guan et al., Curr Neuropharmacol. 2024 Yan et al., J Exp Clin Cancer Res. 2024 |
Antibodies Proteins Kits |
| Forkhead (FOXO) (e.g., FOXO1, FOXO3) | Winged helix TFs, Regulate apoptosis, p300 acetylates FOXO proteins | Diabetes, cancer, aging-related diseases | Wang et al., Life Sci. 2025 Link et al., Methods Mol Biol. 2025 |
|
| HDACs(1-10) | Zn²⁺-dependent, histone/ non-histone deacetlation, transcriptional repression, Antagonize p300 | Cancer (e.g., leukemia, colon, prostate), neurodegeneration, skeletal muscle atrophy, immune disorders | Cheng et al., Eur J Med Chem. 2025 Mazzocchi et al., Brain Behav Immun. 2022 Habibian et al., Cell Signal. 2023 |
|
| HIF‑1α (Hypoxia-Inducible Factor 1α) | Oxygen-sensitive transcription factor, Activates genes involved in hypoxia response, Requires p300/CBP as co-activator to initiate transcription | Cancer (solid tumors, Ischemic diseases, Pulmonary hypertension, Anemia | Zhang et al., Clin Exp Hypertens. 2025 Liu et al., An Acad Bras Cienc. 2023 Li et al., Heliyon. 2024 |
Antibodies Proteins |
| Histones | Linker & core histones, Stabilizes higher-order chromatin structure; represses transcription, helps package DNA, transcriptional regulation. DNA repair, and acetylated by p300 | Altered expression in cancer, autoimmune diseases, DNA repair defects, neurological disorders | Yang et al., Front Immunol. 2024 Erady et al., medRxiv. 2025 Yekta et al., Front Oncol. 2024 |
|
| HMGB1 (High Mobility Group Box 1) | Non-histone chromatin-binding protein, enhances transcription, p300 acetylates HMGB1, especially during stress/inflammation | Sepsis, Cancer, Rheumatoid arthritis, Atherosclerosis, Neurodegenerative diseases (e.g., Alzheimer's) | Lv et al., Front Oncol. 2024 Ho et al., Int Immunopharmacol. 2025 Wei et al., Cell Biol Toxicol. 2025 |
Antibodies |
| JMJD1A (Jumonji domain-containing protein 1A / KDM3A) | Histone demethylase, (JmjC-domain family), promotes transcriptional activation by removing repressive marks, functionally cooperates with p300 | Metabolic syndrome, Obesity, Prostate & testicular cancer, Male infertility, Cardiac hypertrophy | Sui et al., Mol Cancer Res. 2021 Han et al., Biochem Genet. 2025 |
Proteins |
| NF‑κB (p65) | Transcription factor (Rel family), Regulates immune response, cell survival, and stress responses. p300 binds to and acetylates p65, enhancing its transcriptional activity and stability | Cancer (e.g., lymphoma, breast, colon), Autoimmune diseases, Chronic inflammation, Neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s) | Rodrigues de Castro et al., J Cell Physiol. 2024 Soelter et al., Cell Commun Signal. 2024 |
|
| p300 | Acts as a histone acetyltransferase (HAT), Acetylates lysine residues on histone tails (e.g., H3K27ac), transcriptional co-activator & modulates chromatin structure to enhance gene expression | Mutations found in various cancers, Rubinstein Syndrome, Neurodevelopmental Disorders, Inflammation & Viral Infections | Chen et al., J Neuropathol Exp Neurol. 2025 Liu et al., bioRxiv 2025 Wei et al., Cell Biol Toxicol. 2025 |
|
| p53 | Tumor suppressor transcription factor, Regulates DNA damage response, p300 directly binds and acetylates p53 enhancing its transcriptional activity | Almost all major cancers (mutated in >50% of human tumors), Li-Fraumeni syndrome, Neurodegenerative diseases (e.g., Alzheimer’s) | Chen et al., Oncogene. 2025 Liu et al., Nat Rev Mol Cell Biol. 2025 |
Kits |
| Sirtuins: (SIRT1–7) | NAD⁺-dependent deacetylases, Metabolic and stress response regulators, SIRT1 deacetylates p300 | Aging, metabolic diseases, cancer, cardiovascular diseases | Ding et al., Circ Res. 2025 Zhra et al., Cells. 2025 Yu et al., Front Oncol. 2024 |
|
| SMAD2/3 | TGF-β signaling effectors, fibrosis, p300 acetylates and stabilizes SMADs, enhancing target gene, expression | Fibrosis, cancer, Marfan-like syndromes | Gu et al., Mol Ther. 2024 Chen et al., J Am Heart Assoc. 2025 |
Antibodies Proteins |
| STAT1 | Transcription factor, Promote inflammation, cell survival, proliferation, most stats are acelytated by p300 | Many cancers (breast, lung, lymphoma), autoimmune diseases, chronic inflammation | Hadzic et al., N Engl J Med. 2024 Chen et al., Biomaterials. 2025 Yang et al., J Adv Res. 2025 |
|
| TAF1 | Largest subunit of TFIID, Functions as a scaffold and kinase. Cooperates with p300 at promoters for transcription initiation; p300 acetylation of histones facilitates TFIID binding | Neurodevelopmental disorders; cancer | Chen et al., Mol Cancer Ther. 2025 Burgos et al., bioRxiv 2025 |
Proteins |
Additional Resources
- [Blog] Targeting the CBP/p300: A Novel Therapeutic Approach to SMARCB1-Deficient Tumors?
- [Blog] CBP and p300 Lead an Epigenetic Response in Alzheimer's Disease-affected Neurons
- [Blog] Monkeying Around with Transcription? How CHMP5 Promotes Leukemia Development via BRD4 and p300
