Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II
Year: 2016
Type: article
Abstract: The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkw571
Institutions: Xiamen University, University of Illinois Urbana-Champaign
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Awards: G1045161306, G1123043014, G1262555851, G1943689128, G2033899444, G233370561, G2621288770, G3051007241, G3479885705, G4665241992, G5301307736, G5401086813, G5537519703, G5952781527, G614318509, P-TEFb重活化调控机制及其对细胞周期的影响, G6699506941, P-TEFb识别并调控特异基因转录延伸重启机制, G7357316226, G74122498, G7624720968, Brd4应激活化的信号和分子调控机制及其作为抗肿瘤靶点的前景, G8357599891, G8458199910, G8848551010, G9000013785, G9000294327, G95745863
OpenAlex ID: W2469370169