H3K4me3 regulates RNA polymerase II promoter-proximal pause-release.
H3K4me3 regulates RNA polymerase II promoter-proximal pause-release.
复制标题
H3K4ME3调节RNA聚合酶II启动子释放释放。
DOI：
10.1038/s41586-023-05780-8
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发表时间：
2023-03
期刊：
影响因子：
64.8
通讯作者：
Helin, Kristian
中科院分区：
文献类型：
--
作者：
Wang, Hua;Fan, Zheng;Shliaha, Pavel V.;Miele, Matthew;Hendrickson, Ronald C.;Jiang, Xuejun;Helin, Kristian
Trimethylation of histone H3 lysine 4 (H3K4me3) is associated with transcriptional start sites and has been proposed to regulate transcription initiation. However, redundant functions of the H3K4 SET1/COMPASS methyltransferase complexes complicate the elucidation of the specific role of H3K4me3 in transcriptional regulation. 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. 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 pausing and slower elongation
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影响因子：
16.6
作者：
Hughes, Amy L.;Szczurek, Aleksander T.;Kelley, Jessica R.;Lastuvkova, Anna;Turberfield, Anne H.;Dimitrova, Emilia;Blackledge, Neil P.;Klose, Robert J.
通讯作者：
Klose, Robert J.
影响因子：
14.8
作者：
Hung V;Udeshi ND;Lam SS;Loh KH;Cox KJ;Pedram K;Carr SA;Ting AY
通讯作者：
Ting AY
影响因子：
16
作者：
Caizzi, Livia;Monteiro-Martins, Sara;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
64.5
作者：
Levine M
通讯作者：
Levine M
影响因子：
4.6
作者：
Bledau, Anita S.;Schmidt, Kerstin;Anastassiadis, Konstantinos
通讯作者：
Anastassiadis, Konstantinos