Histone acetyltransferase p300 (EP300) (EP300)

Histone acetyltransferase p300 (EP300) is a critical transcriptional coactivator that regulates gene expression by modifying chromatin structure. It functions as both an epigenetic writer through its histone acetyltransferase (HAT) domain and an epigenetic reader via its bromodomain, which recognizes acetylated lysine residues on histones [Visualized Cancer Medicine, Koç University]. EP300 is essential for various cellular processes, including cell cycle progression, differentiation, and DNA repair [PMC]. In many cancers, such as metastatic castration-resistant prostate cancer and hematologic malignancies, EP300 is hijacked to drive the expression of key oncogenes like the androgen receptor (AR), MYC, and IRF4 [Opna Bio, PubMed, eLife]. Small-molecule inhibitors targeting the EP300 bromodomain, such as inobrodib (CCS1477), work by displacing the protein from enhancers, thereby suppressing oncogenic transcriptional programs [Blood, Cancer Research UK]. Clinical development of these inhibitors faces challenges such as dose-limiting thrombocytopenia and the high structural similarity between EP300 and its paralog, CREB-binding protein (CBP) [ResearchGate, YouTube, AACR].

Other names

p300KAT3BE1A-associated protein p300CREBBP-related protein

Bromodomain inhibition (competitive binding to the acetyl-lysine binding pocket, preventing chromatin recruitment and subsequent transcriptional activation of oncogenic drivers).