Yang X, Lamia K A, Evans R M
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Cold Spring Harb Symp Quant Biol. 2007;72:387-94. doi: 10.1101/sqb.2007.72.058.
As ligand-dependent transcription factors, the nuclear receptor superfamily governs a remarkable array of rhythmic physiologic processes such as metabolism and reproduction. To provide a "molecular blueprint" for nuclear receptor function in circadian biology, we established a diurnal expression profile of all mouse nuclear receptors in critical metabolic tissues. Our finding of broad expression and tissue-specific oscillation of nuclear receptors along with their key target genes suggests that diurnal nuclear receptor expression may contribute to established rhythms in metabolic physiology and that nuclear receptors may be involved in coupling peripheral circadian clocks to divergent metabolic outputs. Conversely, nuclear receptors may serve peripheral clock input pathways, integrating signals from the light-sensing central clock in the suprachiasmatic nucleus and other environmental cues, such as nutrients and xenobiotics. Interplay between the core circadian clock and nuclear receptors may define a large-scale signaling network that links biological timing to metabolic physiology.
作为配体依赖性转录因子，核受体超家族调控着一系列显著的节律性生理过程，如新陈代谢和生殖。为了提供核受体在昼夜节律生物学中功能的“分子蓝图”，我们建立了关键代谢组织中所有小鼠核受体的昼夜表达谱。我们发现核受体及其关键靶基因具有广泛的表达和组织特异性振荡，这表明昼夜核受体表达可能有助于代谢生理学中既定的节律，并且核受体可能参与将外周生物钟与不同的代谢输出相耦合。相反，核受体可能充当外周生物钟输入途径，整合来自视交叉上核中光感应中央生物钟的信号以及其他环境线索，如营养物质和外源性物质。核心昼夜节律钟与核受体之间的相互作用可能定义一个将生物定时与代谢生理学联系起来的大规模信号网络。
