Transcriptional architecture and chromatin landscape of the core circadian clock in mammals.

Transcriptional architecture and chromatin landscape of the core circadian clock in mammals.
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哺乳动物核心昼夜节律的转录结构和染色质景观。

DOI:
10.1126/science.1226339
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发表时间:
2012-10-19
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Takahashi JS
Takahashi JS
中科院分区:
其他
文献类型:
--
作者:
Koike N;Yoo SH;Huang HC;Kumar V;Lee C;Kim TK;Takahashi JS

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哺乳动物的生物钟涉及一个转录反馈环,其中CLOCK和BMAL 1激活Period和Cryptochrome基因,然后反馈并抑制它们自己的转录。我们已经询问了小鼠肝脏基因组规模上的昼夜节律转录调控环的转录结构,并发现转录因子结合,RNA聚合酶II(RNAPII)招募,RNA表达和染色质状态的定型,时间依赖性模式。我们发现,生物钟的昼夜转录周期由三个不同的阶段组成-平衡状态,协调从头转录激活状态,和抑制状态。有趣的是,只有22%的mRNA循环基因是由从头转录驱动的,这表明转录和转录后机制都是哺乳动物生物钟的基础。我们还发现RNAPII募集和染色质重塑的昼夜节律调节发生在全基因组范围内,远远大于以前通过基因表达谱所看到的。
The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases — a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Interestingly only 22% of mRNA cycling genes are driven by de novo transcription, suggesting that both transcriptional and post-transcriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.
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