BRD4 Protein, Human (His-Flag)

BRD4 protein functions as a chromatin reader, specifically recognizing and binding acetylated histones, thereby playing a crucial role in transmitting epigenetic memory across cell divisions and regulating transcription. It remains associated with acetylated chromatin throughout the cell cycle, preserving the acetylated chromatin status and maintaining high-order chromatin structure, contributing to epigenetic memory for postmitotic G1 gene transcription. During interphase, BRD4 is pivotal in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Additionally, it collaborates with JMJD6 in recruiting the P-TEFb complex to distal enhancers, known as anti-pause enhancers, displacing negative regulators and transforming P-TEFb into an active form that can phosphorylate the C-terminal domain of RNA polymerase II. BRD4 also acts as an atypical protein kinase, promoting phosphorylation of 'Ser-2' of the C-terminal domain of RNA polymerase II. Beyond histones, BRD4 recognizes and binds acetylated RELA, facilitating the recruitment of the P-TEFb complex and activating NF-kappa-B. Furthermore, it acts as a regulator of p53/TP53-mediated transcription, being recruited to specific target promoters upon phosphorylation by CK2. In the DNA damage response pathway, BRD4 acts as a chromatin insulator, inhibiting DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones and limiting the spreading of histone H2AX/H2A.x phosphorylation. These diverse functions underscore the versatile role of BRD4 in epigenetic regulation, transcriptional control, and maintenance of chromatin structure.