Regulation of Pol II Pausing Is Involved in Daily Gene Transcription in the Mouse Liver
Regulation of Pol II Pausing Is Involved in Daily Gene Transcription in the Mouse Liver
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Pol II 暂停的调节涉及小鼠肝脏的日常基因转录
DOI：
10.1177/0748730418779526
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发表时间：
2018-05
影响因子：
3.5
通讯作者：
Li XD
中科院分区：
文献类型：
--
作者：
Zhu Jialou;Li Chengwei;Gong Changxia;Li Xiaodong;Li Chengwei;Li XD
生物钟协调基因表达的节奏。基因转录水平的调节对分子和细胞节律是必不可少的。POL II暂停释放是转录调控的关键步骤。然而，在日常转录过程中，POL II暂停释放是否以及如何受到调控还没有确定。在这项研究中，我们在小鼠肝脏中进行了全天的POL II CHIP-SEQ，并定量分析了转录起始部位(TSS)区域和基因体内的结合信号。我们经常发现TSS附近的Pol II([Pol II]TSS，停顿的Pol II)与基因组中基因体([Pol II]GB，转录Pol II)之间的不一致变化，只有[Pol II]GB总是反映时钟和时钟控制基因的转录。因此，7000多个基因的POLII迁移率显示出显著的每日变化(1.5倍)。因此，在小鼠肝脏中广泛存在对Pol II暂停的调节。有趣的是，基因转录节律呈双峰型分布。约400个基因的转录在ZT0附近达到峰值，与全基因组范围内[Pol II]TSS和旅行比(Tr.)的增加相一致。~300个其他基因的转录在12h后达到高峰，此时[Pol II]TSS和TR值整体下降。针对前起始复合体(PIC)组分TATA结合蛋白(TBP)的ChIP-SEQ表明，Pol II的招募主要在转录输出中起间接作用，转录终止和暂停释放在决定启动的Pol II的命运及其暂停状态中起着重要作用。综上所述，我们的结果揭示了POLII暂停控制在调节基因转录的时间输出中的关键作用，尽管作用复杂。
The circadian clock orchestrates gene expression rhythms. Regulation at the level of gene transcription is essential for molecular and cellular rhythms. Pol II pause release is a critical step of transcription regulation. However, whether and how Pol II pause release is regulated during daily transcription have not been characterized. In this study, we performed Pol II ChIP-seq across the day in the mouse liver and quantitatively analyzed binding signals within the transcription start site (TSS) region and the gene body. We frequently found discordant changes between Pol II near the TSS ([Pol II]TSS, paused Pol II) and that within the gene body ([Pol II]GB, transcribing Pol II) across the genome, with only [Pol II]GB always reflecting transcription of clock and clock-controlled genes. Accordingly, Pol II traveling ratios of more than 7000 genes showed significant daily changes (>1.5-fold). Therefore, there is widespread regulation of Pol II pausing in the mouse liver. Interestingly, gene transcription rhythms exhibited a bimodal phase distribution. The transcription of ~400 genes peaked near ZT0, coincident with a genome-wide increase in [Pol II]TSS and traveling ratio (TR). The transcription of ~300 other genes peaked ~12 h later, when there was a global decrease in [Pol II]TSS and TR. ChIP-seq against TATA-binding protein (Tbp), a preinitiation complex (PIC) component, revealed that Pol II recruitment mainly played an indirect role in transcriptional output, with transcriptional termination and pause release functioning prominently in determining the fate of initiated Pol II and its pausing status. Taken together, our results revealed a critical, albeit complex role of Pol II pausing control in regulating the temporal output of gene transcription.
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