Nakahata Yasukazu, Grimaldi Benedetto, Sahar Saurabh, Hirayama Jun, Sassone-Corsi Paolo
Department of Pharmacology, School of Medicine, University of California, Irvine, California 92697, USA.
Curr Opin Cell Biol. 2007 Apr;19(2):230-7. doi: 10.1016/j.ceb.2007.02.016. Epub 2007 Feb 20.
Circadian rhythms govern several fundamental physiological functions in almost all organisms, from prokaryotes to humans. The circadian clocks are intrinsic time-tracking systems with which organisms can anticipate environmental changes and adapt to the appropriate time of day. In mammals, circadian rhythms are generated in pacemaker neurons within the suprachiasmatic nuclei (SCN), a small area of the hypothalamus, and are entrained by environmental cues, principally light. Disruption of these rhythms can profoundly influence human health, being linked to depression, insomnia, jet lag, coronary heart disease and a variety of neurodegenerative disorders. It is now well established that circadian clocks operate via transcriptional feedback autoregulatory loops that involve the products of circadian clock genes. Furthermore, peripheral tissues also contain independent clocks, whose oscillatory function is orchestrated by the SCN. The complex program of gene expression that characterizes circadian physiology involves dynamic changes in chromatin transitions. These remodeling events are therefore of great importance to ensure the proper timing and extent of circadian regulation. How signaling influences chromatin remodeling through histone modifications is therefore highly relevant in the context of circadian oscillation. Recent advances in the field have revealed unexpected links between circadian regulators, chromatin remodeling and cellular metabolism.
昼夜节律几乎在所有生物（从原核生物到人类）中调控着多种基本生理功能。生物钟是内在的时间追踪系统，生物体可借此预测环境变化并适应一天中的合适时间。在哺乳动物中，昼夜节律由下丘脑一个小区域——视交叉上核（SCN）内的起搏器神经元产生，并受环境线索（主要是光）的调节。这些节律的紊乱会深刻影响人类健康，与抑郁症、失眠、时差反应、冠心病及多种神经退行性疾病有关。现在已经明确，生物钟通过涉及生物钟基因产物的转录反馈自动调节环发挥作用。此外，外周组织也含有独立的时钟，其振荡功能由SCN协调。表征昼夜生理的复杂基因表达程序涉及染色质转变的动态变化。因此，这些重塑事件对于确保昼夜调节的正确时间和程度至关重要。因此，在昼夜振荡的背景下，信号如何通过组蛋白修饰影响染色质重塑具有高度相关性。该领域的最新进展揭示了昼夜调节因子、染色质重塑和细胞代谢之间意想不到的联系。
