ArticleNucleic acids research2016
Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 91 citations in OpenAlex.
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- Active Field Theory Approach to Explain Size Control of Transcriptional Condensates.Macromolecular bioscience · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Nonlinearities and Switch-Like Behavior in Gene Expression: From Genetics to Biochemistry and Back.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Multisite Threonine Phosphorylation in the SPT5 C-Terminal Region 1 Enables Sequence-Dependent Regulation without Global Structural Remodeling.The journal of physical chemistry. B · 2026Article
- Single-molecule imaging reveals RNA polymerase II dynamics and TAF1-dependent promoter-proximal pause release.Nature communications · 2026Article
- The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate.Annual review of biochemistry · 2026Review
- MED1 IDR deacetylation controls stress responsive genes through RNA Pol II recruitment.Nature chemical biology · 2026Article
- SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes.Science advances · 2025Article
- The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII.Journal of molecular biology · 2025Review
- Toward structural understanding of eukaryotic transcription elongation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- ARF alters PAF1 complex integrity to selectively repress oncogenic transcription programs upon p53 loss.Molecular cell · 2024Article
- Mechanisms and Functions of the RNA Polymerase II General Transcription Machinery during the Transcription Cycle.Biomolecules · 2024Review
- Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation.Journal of molecular cell biology · 2024Article
- MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia.Nature communications · 2023Article
- Distinct layers of BRD4-PTEFb reveal bromodomain-independent function in transcriptional regulation.Molecular cell · 2023Article
- The YEATS domain epigenetic reader proteins ENL and AF9 and their therapeutic value in leukemia.Experimental hematology · 2023Review
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription.Biomolecules · 2023Article
- Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.