Sahar Saurabh, Sassone-Corsi Paolo
Center for Epigenetics and Metabolism, School of Medicine, University of California, Irvine, CA 92697, USA.
Handb Exp Pharmacol. 2013(217):29-44. doi: 10.1007/978-3-642-25950-0_2.
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.
表观遗传调控，包括DNA甲基化和组蛋白修饰，可导致染色质重塑和基因表达调控。染色质重塑构成了转导信号（如光照或营养可用性）的关键界面，以及细胞如何解读这些信号以产生转录的允许或沉默状态。CLOCK-BMAL1介导的生物钟调控基因（CCGs）激活与它们启动子处组蛋白修饰的昼夜节律变化相关联。几种染色质修饰因子，如去乙酰化酶SIRT1和HDAC3或甲基转移酶MLL1，已被证明以昼夜节律的方式被招募到CCGs的启动子上。有趣的是，核心生物钟机制的核心元件，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因子的情况下，CCGs的节律性表达被消除。在这里，我们将讨论证明染色质重塑处于昼夜节律与代谢和细胞增殖调控交叉点的证据。
