Two faces of brd4: mitotic bookmark and transcriptional lynchpin

Abstract

The bromodomain protein BRD4 links cell cycle and transcription, bookmarking active genes during mitosis and serving as a scaffold for transcription factors. Our recent discovery that BRD4 is a RNA Polymerase II CTD kinase identifies a novel transcriptional function. Here we discuss our model in the context of current knowledge.

Keywords: Atypical kinase; BET protein; BRD4; CTD kinase; P-TEFb; RNA Polymerase II.

Figure 1. Model of BRD4 function in cell cycle and gene transcription. During mitosis (upper left), BRD4 functions as a G1 gene bookmark by binding to acetylated chromatin, as a PTEFb recruiter and chromatin de-compacter. During interphase (upper right), it recruits PTEFb to RNAP II, either directly binding chromatin or dimerizing with chromatin-bound BRD4, thereby activating both post mitotic and interphase transcription. During transcription initiation (lower panel), direct and indirect interactions among the CTD kinases, including BRD4, initially keeps their activity in check, with the release of their activities as the transcription complexes proceeds. BRD4 plays a central role in this cross-talk of the CTD kinases.