Coupling circadian rhythms of metabolism and chromatin remodelling.
Coupling circadian rhythms of metabolism and chromatin remodelling.
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DOI：
10.1111/dom.12509
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Sassone-Corsi P
中科院分区：
文献类型：
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作者：
Masri S;Orozco-Solis R;Aguilar-Arnal L;Cervantes M;Sassone-Corsi P
生物钟控制着哺乳动物的多种神经、内分泌、行为和生理反应。这种控制在很大程度上是在转录水平上对以循环方式表达的基因施加的。一种高度专业化的转录机制，以反馈自动调节环中组织的时钟调节因子为基础，管理着基因组的很大一部分。这些基因表达的振荡与染色质重塑的关键事件平行，染色质重塑似乎为昼夜节律提供了可塑性。具体地说，依赖NAD+的脱乙酰酶SIRT1和SIRT6与基因表达的昼夜调控有关。这一点以及其他积累的证据表明，昼夜节律的表观基因组似乎与细胞代谢过程有密切的联系，并且具有显著的可塑性，表明对营养挑战的重新编程。除了SIRT1和SIRT6，许多染色质重构体参与了时钟控制，包括组蛋白H3K4三甲基转移酶MLL1。破译新陈代谢、表观遗传控制和昼夜节律反应的分子机制将为治疗干预的创新策略提供宝贵的见解。
The circadian clock controls a large variety of neuronal, endocrine, behavioral and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodeling that appear to provide plasticity to circadian regulation. Specifically, the NAD+-dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodelers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valauble insights towards innovative strategies of therapeutic intervention.