CREB-binding protein and E1A-binding protein p300 bromodomain (CBP and p300 bromodomains)

The CREB-binding protein (CBP, gene name CREBBP) and E1A-binding protein p300 (gene name EP300) are closely related, multifunctional transcriptional coactivators that regulate chromatin dynamics and gene expression through intrinsic histone acetyltransferase (HAT) activity. Each harbors a single conserved bromodomain, a structural motif of about 110 amino acids that serves as an “acetyl-lysine reader”—binding specifically to acetylated lysine residues on histone tails and, potentially, non-histone substrates[1][2][3][6]. The bromodomain is required for recruitment to acetylated chromatin, enabling CBP/p300 to function as coactivators for transcription factors, integrate multiple signals, and activate gene expression involved in cell proliferation, differentiation, apoptosis, immune responses, and development[2][3][6][8]. Dysregulation of CBP/p300 and their bromodomains is implicated in various cancers and other diseases, making them therapeutic targets for selective bromodomain inhibitors, which are in development as cancer therapeutics but may carry the risk of systemic toxicity due to the essential, pleiotropic roles of CBP/p300[6][7].

Other names

CBP bromodomainp300 bromodomainCREBBP bromodomainEP300 bromodomainKAT3A bromodomain (CBP)KAT3B bromodomain (p300)

Inhibition of bromodomain blocks recognition of acetylated lysines on histones - Disrupts coactivator recruitment to chromatin - Suppresses transcriptional activation by blocking coactivator-dependent gene expression[5][7]