Aguilar-Arnal Lorena, Sassone-Corsi Paolo
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA 92697.
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA 92697
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6863-70. doi: 10.1073/pnas.1411264111. Epub 2014 Nov 5.
Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional-translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear "hubs" of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control.
昼夜节律以约24小时的周期驱动着多种生理和行为功能的时间组织。这种控制是通过一个复杂的基因表达程序实现的。在哺乳动物中，分子时钟机制由相互连接的转录-翻译反馈环组成，这些反馈环最终确保数千个基因以组织特异性的方式进行适当的振荡。为了实现昼夜节律转录控制，染色质重塑因子通过为表观基因组提供适当的振荡来服务于时钟机制。最近的研究结果揭示了昼夜节律相互作用组的存在，即基因组拓扑结构的核“枢纽”，在那里协调表达的昼夜节律基因以时空特异性的方式进行物理相互作用。因此，似乎存在一种昼夜节律核景观，其与代谢途径和时钟调节因子的相互作用转化为特定的转录程序。解读将昼夜节律时钟机制与核景观联系起来的分子机制，将揭示尚未探索的将细胞代谢与表观遗传控制联系起来的途径。
