We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive.

Nov 21, 2024 · JNK-mediated BRD4 functional switching induces CD8 expression in thymocytes and epithelial-to-mesenchymal transition (EMT) in prostate cancer cells. These findings elucidate the mechanism by which BRD4 transitions from a chromatin regulator to a …

Aug 17, 2023 · Although BRD4-PTEFb can associate with chromatin through acetyl recognition, our results indicate that a distinct, active BRD4-PTEFb population functions to regulate transcription independently of bromodomain-mediated chromatin association. These findings may enable more effective pharmaceutical modulation of BRD4-PTEFb activity.

Aug 19, 2005 · Correlating with changes in promoter activity, Ser2 CTD phosphorylation was enhanced by Brd4 overexpression and reduced by Brd4 underexpression. This correlation indicates that Brd4 expression levels are an important determinant of the functionality of P-TEFb.

Bromodomain protein 4 (BRD4) is a transcriptional and epigenetic regulator that plays a pivotal role in cancer and inflammatory diseases. BRD4 binds and stays associated with chromatin during mitosis, bookmarking early G1 genes and reactivating transcription after mitotic silencing.

Our findings suggest that BRD4-driven Pol II phosphorylation at serine 2 plays an important role in regulating lineage-specific gene transcription in human CD4+ T cells. Regulation of gene transcription occurs at both initiation and elongation phases (1, 2).

Mar 16, 2017 · In parallel, Brd4 temporally controls RNA polymerase II (Pol II) processivity during transcription elongation through cyclin T1 and Cdk9 recruitment and Pol II Ser2 phosphorylation. Collectively, our study uncovers both separate and interdependent Brd2 and Brd4 functions in potentiating the genetic program required for Th17 cell development and ...

Aug 20, 2021 · We locate the BRD4 kinase activity within the BRD4 region spanning the BD2-B-BID domains. The BRD4 kinase activity behaves with classical Michaelis–Menten kinetics both to autophosphorylate and to trans-phosphorylate its CTD and TAF7 substrates. In vivo phosphorylation of the CTD at Ser2 by BRD4 depends on the kinase activity. Interestingly ...

BRD4 has been implicated in the regulation of Pol II transcription elongation [49,50]. BRD4 belongs together with BRD2, BRD3 and BRDT to the mammalian BET bromodomain protein family [49,51,52].

The functional role of BRD4 in vivo as the primary CTD Ser2 kinase was confirmed by our finding that preventing BRD4 from being recruited to the transcription site, or its siRNA knockdown, reduces Ser2 phosphorylation and nascent RNA levels whereas knockdown of PTEFb/CDK9 had only a minimal effect. 11