核受体共抑制因子-1（Ncor1）是组蛋白脱乙酰基酶-3（Hdac3）的一个激发因子，是胚胎生成所必需的，但其生理功能却不知道。
现在，用缺失Ncor1的基因剔除小鼠所做实验表明，Ncor1-Hdac3相互作用的破坏引起时钟基因的异常调控，导致异常节律行为——睡眠-清醒周期接近23小时，而不是正常的24小时。由于能量消耗增加，这些小鼠还比正常情况下更瘦，对胰岛素更敏感。在活体中，一个功能性Ncor1-Hdac3复合物的失去，会改变几个代谢基因的振荡模式，说明代谢的节律性调控是正常能量平衡的关键。以Ncor1-Hdac3酶为治疗目标，在营养压力型疾病如肥胖症和糖尿病的治疗中，可能是一种具有高度特异性的干预手段。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 456, 997-1000 (18 December 2008) | doi:10.1038/nature07541
Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology
Theresa Alenghat1,2, Katherine Meyers1,2, Shannon E. Mullican1,2, Kirstin Leitner1,2, Adetoun Adeniji-Adele3, Jacqueline Avila1,2, Maja Buan3, Rexford S. Ahima1,2, Klaus H. Kaestner2,3 & Mitchell A. Lazar1,2
1 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine,
2 The Institute for Diabetes, Obesity, and Metabolism, and,
3 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Rhythmic changes in histone acetylation at circadian clock genes suggest that temporal modulation of gene expression is regulated by chromatin modifications1, 2, 3. Furthermore, recent studies demonstrate a critical relationship between circadian and metabolic physiology4, 5, 6, 7. The nuclear receptor corepressor 1 (Ncor1) functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (Hdac3)8. Lack of Ncor1 is incompatible with life, and hence it is unknown whether Ncor1, and particularly its regulation of Hdac3, is critical for adult mammalian physiology9. Here we show that specific, genetic disruption of the Ncor1–Hdac3 interaction in mice causes aberrant regulation of clock genes and results in abnormal circadian behaviour. These mice are also leaner and more insulin-sensitive owing to increased energy expenditure. Unexpectedly, loss of a functional Ncor1–Hdac3 complex in vivo does not lead to sustained increases in known catabolic genes, but instead significantly alters the oscillatory patterns of several metabolic genes, demonstrating that circadian regulation of metabolism is critical for normal energy balance. These findings indicate that activation of Hdac3 by Ncor1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology.
