H3K4me3 regulates RNA polymerase II promoter-proximal pause-release.

Autor: Wang H; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fan Z; The Institute of Cancer Research, London, United Kingdom.; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, Copenhagen, Denmark., Shliaha PV; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Miele M; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hendrickson RC; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jiang X; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Helin K; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kristian.helin@icr.ac.uk.; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kristian.helin@icr.ac.uk.; The Institute of Cancer Research, London, United Kingdom. kristian.helin@icr.ac.uk.; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. kristian.helin@icr.ac.uk.; The Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, Copenhagen, Denmark. kristian.helin@icr.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Mar; Vol. 615 (7951), pp. 339-348. Date of Electronic Publication: 2023 Mar 01.
DOI: 10.1038/s41586-023-05780-8
Abstrakt: Trimethylation of histone H3 lysine 4 (H3K4me3) is associated with transcriptional start sites and has been proposed to regulate transcription initiation 1,2 . However, redundant functions of the H3K4 SET1/COMPASS methyltransferase complexes complicate the elucidation of the specific role of H3K4me3 in transcriptional regulation 3,4 . Here, using mouse embryonic stem cells as a model system, we show that acute ablation of shared subunits of the SET1/COMPASS complexes leads to a complete loss of all H3K4 methylation. Turnover of H3K4me3 occurs more rapidly than that of H3K4me1 and H3K4me2 and is dependent on KDM5 demethylases. Notably, acute loss of H3K4me3 does not have detectable effects on transcriptional initiation but leads to a widespread decrease in transcriptional output, an increase in RNA polymerase II (RNAPII) pausing and slower elongation. We show that H3K4me3 is required for the recruitment of the integrator complex subunit 11 (INTS11), which is essential for the eviction of paused RNAPII and transcriptional elongation. Thus, our study demonstrates a distinct role for H3K4me3 in transcriptional pause-release and elongation rather than transcriptional initiation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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