RSC primes the quiescent genome for hypertranscription upon cell-cycle re-entry.
RSC primes the quiescent genome for hypertranscription upon cell-cycle re-entry.
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DOI：
10.7554/elife.67033
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发表时间：
2021-05-27
期刊：
影响因子：
7.7
通讯作者：
Tsukiyama T
中科院分区：
文献类型：
--
作者：
Cucinotta CE;Dell RH;Braceros KC;Tsukiyama T
静止是一种可逆的G0状态，对分化、再生、干细胞更新和免疫细胞激活至关重要。对于长期生存来说，静止的染色质是致密的、低乙酰化的、转录不活跃的。转录如何在细胞周期重新进入时被激活尚不清楚。在这里，我们报告了在静止退出的第一分钟内强劲、广泛的转录。在静止期间，染色质重塑酶RSC已经与静止退出时诱导的基因结合。RSC耗竭导致严重的静止退出缺陷：RNA聚合酶II(Pol II)载量整体下降，Pol II在转录起始点聚集，异位上游位点启动，反义转录异常。这些现象是由于POL II高度强健的转录和启动子区域和基因体中严重的染色质缺陷所致。总之，这些结果揭示了多种机制，RSC通过这些机制促进了大规模、快速的基因表达的启动和维持，尽管染色质处于全球抑制状态。
Quiescence is a reversible G0 state essential for differentiation, regeneration, stem-cell renewal, and immune cell activation. Necessary for long-term survival, quiescent chromatin is compact, hypoacetylated, and transcriptionally inactive. How transcription activates upon cell-cycle re-entry is undefined. Here we report robust, widespread transcription within the first minutes of quiescence exit. During quiescence, the chromatin-remodeling enzyme RSC was already bound to the genes induced upon quiescence exit. RSC depletion caused severe quiescence exit defects: a global decrease in RNA polymerase II (Pol II) loading, Pol II accumulation at transcription start sites, initiation from ectopic upstream loci, and aberrant antisense transcription. These phenomena were due to a combination of highly robust Pol II transcription and severe chromatin defects in the promoter regions and gene bodies. Together, these results uncovered multiple mechanisms by which RSC facilitates initiation and maintenance of large-scale, rapid gene expression despite a globally repressive chromatin state.