FEATURES

FAMILY

DESCRIPTION

Also known as BRD4_HUMAN, BRD4, HUNK1. Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation (PubMed:20871596, PubMed:23086925, PubMed:23317504, PubMed:29176719, PubMed:29379197). Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:22334664, PubMed:23317504, PubMed:23589332). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504)., Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. Interacts with p53/TP53; the interaction is direct (PubMed:23317504). Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex (PubMed:16109376, PubMed:16109377, PubMed:23317504, PubMed:24360279). Interacts with RELA (when acetylated at 'Lys-310') (PubMed:19103749). Interacts (via NET domain) with NSD3, CHD4, BICRA and ATAD5 (PubMed:21555454, PubMed:29176719). The interaction with BICRA bridges BRD4 to the GBAF complex (PubMed:16109376, PubMed:16109377, PubMed:19103749, PubMed:21555454, PubMed:23317504, PubMed:29374058). Interacts (via NET domain) with JMJD6 (via JmjC and N-terminal domains); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers (PubMed:21555454, PubMed:24360279, PubMed:29176719). Interacts with NSD3 (PubMed:29176719). Interacts with NIPBL (By similarity).

EXTERNAL LINKS

BRD4

Bromodomain-containing protein 4

Structural Ligandability

Domains Chains

0 chains assessed

1 chain not associated with a domain

BRD4

Structural Ligandability

Domains Chains

Distribution