Recombinant Human Brd4 protein (Tagged)

일반 정보

기능

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).. Isoform B. 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.

서열 유사성

Belongs to the BET family.

Post-translational modifications

Phosphorylation by CK2 disrupt the intramolecular binding between the bromo domain 2 and the NPS region and promotes binding between the NPS and the BID regions, leading to activate the protein and promote binding to acetylated histones. In absence of phosphorylation, BRD4 does not localize to p53/TP53 target gene promoters, phosphorylation promoting recruitment to p53/TP53 target promoters.