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小鼠肝脏每日基因转录过程中RNA聚合酶II暂停的调控

Regulation of Pol II Pausing during Daily Gene Transcription in Mouse Liver.

作者信息

Xu Wei, Li Xiaodong

机构信息

College of Life Sciences, Wuhan University, Wuhan 430072, China.

出版信息

Biology (Basel). 2023 Aug 9;12(8):1107. doi: 10.3390/biology12081107.

DOI:10.3390/biology12081107
PMID:37626993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10452108/
Abstract

Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment, pause release, and premature transcription termination are critical regulatory steps that determine the status of Pol II pausing and transcription output near the transcription start site (TSS) of the promoter. Recently, we showed that Pol II pausing exhibits genome-wide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms by the circadian clock and other transcription factors, and the potential limitations of those results in explaining rhythmic transcription at the TSS. We then discuss our results on the genome-wide characteristics of daily changes in Pol II pausing, the possible regulatory mechanisms involved, and their relevance to future research on circadian transcription regulation.

摘要

细胞自主昼夜节律振荡存在于中枢和各种外周组织中。内在的组织时钟和各种外在信号驱动基因表达节律。转录调控被认为是基因节律的主要驱动力。然而,由于转录在多个步骤受到调控,转录节律是如何产生的仍有待充分阐明。特别是,RNA聚合酶II(Pol II)的募集、暂停释放和过早转录终止是决定Pol II在启动子转录起始位点(TSS)附近暂停状态和转录输出的关键调控步骤。最近,我们发现Pol II暂停在小鼠肝脏的日常转录过程中呈现全基因组范围的变化。在本文中,我们回顾了关于昼夜节律时钟和其他转录因子对转录节律调控的历史及最新研究发现,以及这些结果在解释TSS处节律性转录方面的潜在局限性。然后,我们讨论了关于Pol II暂停每日变化的全基因组特征、可能涉及的调控机制及其与昼夜节律转录调控未来研究的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/4f13dc8f4465/biology-12-01107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/bed41e0ce95a/biology-12-01107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/3b07f0924de7/biology-12-01107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/4f13dc8f4465/biology-12-01107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/bed41e0ce95a/biology-12-01107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/3b07f0924de7/biology-12-01107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/10452108/4f13dc8f4465/biology-12-01107-g003.jpg

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本文引用的文献

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PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII.PGC-1α 通过感知 pre-mRNA 的 CBC 来决定启动子近端暂停的 RNAPII 的命运。
Mol Cell. 2023 Jan 19;83(2):186-202.e11. doi: 10.1016/j.molcel.2022.12.022.
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Integrator is a global promoter-proximal termination complex.整合因子是一个全局促进-近端终止复合物。
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Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1.
在急性 CTCF、cohesin、WAPL 或 YY1 缺失的情况下,增强子-启动子相互作用和转录在很大程度上得以维持。
Nat Genet. 2022 Dec;54(12):1919-1932. doi: 10.1038/s41588-022-01223-8. Epub 2022 Dec 5.
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Xrn2 substrate mapping identifies torpedo loading sites and extensive premature termination of RNA pol II transcription.Xrn2 底物图谱鉴定了 torpedo 的加载位点和 RNA pol II 转录的广泛提前终止。
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Integrator endonuclease drives promoter-proximal termination at all RNA polymerase II-transcribed loci.整联蛋白内切酶驱动所有 RNA 聚合酶 II 转录基因座的启动子近端终止。
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Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver.全面分析小鼠肝脏的昼夜核质转录组。
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Trends Biochem Sci. 2022 Dec;47(12):1009-1022. doi: 10.1016/j.tibs.2022.06.007. Epub 2022 Jul 11.
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