Chromosome dynamics and cellular clocks Many genes undergo daily or circadian changes in their rate of transcription. Kim et al. explored the mechanism by which the circadian clock is linked to chromosome dynamics (see the Perspective by Diettrich Mallet de Lima and Göndör). They used a chromosome conformation capture technique (Hi-C) to identify the interactions of adjacent DNA fragments and determine how DNA looping that altered such interactions changed over daily cycles. The repressive transcription factor Rev-erbα, which functions as part of the mammalian clock mechanism, appears to bind to chromatin and recruit a protein complex that evicts other proteins that enhance looping, thus favoring enhancer-promoter interactions. Science, this issue p. 1274; see also p. 1212 The mechanism by which cellular clocks control chromatin dynamics is explored. Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erbα, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erbα–regulated enhancers and circadian target gene promoters by recruitment of the NCoR-HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.

中文翻译：

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Rev-erbα动态调节染色质环以控制昼夜节律基因转录


染色体动力学和细胞时钟许多基因的转录率每天或昼夜发生变化。金等人。探索了生物钟与染色体动力学联系的机制（参见 Diettrich Mallet de Lima 和 Göndör 的观点）。他们使用染色体构象捕获技术 (Hi-C) 来识别相邻 DNA 片段的相互作用，并确定改变此类相互作用的 DNA 循环在日常周期中如何变化。抑制性转录因子 Rev-erbα 是哺乳动物时钟机制的一部分，它似乎与染色质结合并招募蛋白质复合物，该复合物驱逐其他增强循环的蛋白质，从而有利于增强子-启动子相互作用。科学，本期第 14 页。 1274；另见 p.第1212章 探索细胞时钟控制染色质动态的机制。由于构成分子钟的转录因子控制基因表达的昼夜节律，哺乳动物的生理学表现出 24 小时的周期性。核心时钟转录因子在增强子序列处与基因组结合以调节昼夜节律基因表达，但并非所有结合位点都具有同等功能。我们发现，在小鼠中，肝脏中的昼夜节律基因表达受到增强子和启动子之间有节律的染色质相互作用的控制。 Rev-erbα 是时钟的核心抑制转录因子，通过招募 NCoR-HDAC3 共抑制复合物、组蛋白脱乙酰化和驱逐延伸因子，反对 Rev-erbα 调节的增强子和昼夜节律靶基因启动子之间的功能环形成BRD4 和循环因子 MED1。因此，分子钟的抑制臂通过有节奏地调节染色质环来控制昼夜节律基因转录。