The epigenetic language of circadian clocks.
The epigenetic language of circadian clocks.
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DOI：
10.1007/978-3-642-25950-0_2
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Sassone-Corsi, Paolo
中科院分区：
文献类型：
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作者：
Sahar, Saurabh;Sassone-Corsi, Paolo
表观遗传控制，包括DNA甲基化和组蛋白修饰，导致染色质重塑和调控基因表达。染色质的重塑构成了转导信号的关键界面，例如光或营养物质的可用性，以及细胞如何解释这些信号以产生转录的允许或沉默状态。时钟-BMAL 1介导的时钟控制基因（CCG）的激活与其启动子处组蛋白修饰的昼夜节律变化相关。几种染色质修饰剂，如脱乙酰基酶SIRT 1和HDAC 3或甲基转移酶MLL 1，已被证明以昼夜节律的方式被募集到CCG的启动子。有趣的是，核心时钟机制的核心元件，转录因子CLOCK，也具有组蛋白乙酰转移酶活性。在没有这些染色质修饰剂的情况下，CCG的节律性表达被消除。在这里，我们将讨论的证据表明，染色质重塑是在昼夜节律和代谢和细胞增殖的调节的十字路口。
Epigenetic control, which includes DNA methylation and histone modifications, leads to chromatin remodeling and regulated gene expression. Remodeling of chromatin constitutes a critical interface of transducing signals, such as light or nutrient availability, and how these are interpreted by the cell to generate permissive or silenced states for transcription. CLOCK-BMAL1-mediated activation of clock-controlled genes (CCGs) is coupled to circadian changes in histone modification at their promoters. Several chromatin modifiers, such as the deacetylases SIRT1 and HDAC3 or methyltransferase MLL1, have been shown to be recruited to the promoters of the CCGs in a circadian manner. Interestingly, the central element of the core clock machinery, the transcription factor CLOCK, also possesses histone acetyltransferase activity. Rhythmic expression of the CCGs is abolished in the absence of these chromatin modifiers. Here we will discuss the evidence demonstrating that chromatin remodeling is at the crossroads of circadian rhythms and regulation of metabolism and cellular proliferation.