核受體共抑制因子-1（Ncor1）是組蛋白脫乙?；?3（Hdac3）的一個(gè)激發(fā)因子，是胚胎生成所必需的，但其生理功能卻不知道,。
現(xiàn)在，用缺失Ncor1的基因剔除小鼠所做實(shí)驗(yàn)表明,，Ncor1-Hdac3相互作用的破壞引起時(shí)鐘基因的異常調(diào)控,，導(dǎo)致異常節(jié)律行為——睡眠-清醒周期接近23小時(shí)，而不是正常的24小時(shí),。由于能量消耗增加,，這些小鼠還比正常情況下更瘦,，對(duì)胰島素更敏感。在活體中,，一個(gè)功能性Ncor1-Hdac3復(fù)合物的失去,，會(huì)改變幾個(gè)代謝基因的振蕩模式，說明代謝的節(jié)律性調(diào)控是正常能量平衡的關(guān)鍵,。以Ncor1-Hdac3酶為治療目標(biāo),，在營(yíng)養(yǎng)壓力型疾病如肥胖癥和糖尿病的治療中，可能是一種具有高度特異性的干預(yù)手段,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
