核受体核心压缩剂和基因素脱乙酶3控制昼夜代谢生理学
Theresa Alenghat1, Katherine Meyers, Shannon E Mullican
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nature
|November 28, 2008
概括
在小鼠中破坏Ncor1-Hdac3相互作用会影响昼夜节律和新陈代谢. 这种表观遗传调节是能量平衡和正常生理功能的关键.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 时间生物学 时间生物学
- 代谢生理学 代谢生理学
背景情况:
- 昼夜节律涉及节律性基因表达,这种基因表达由染色质修饰调节,如基因素乙化.
- 核受体核心压缩剂1 (Ncor1) 激活了基因素脱乙酶3 (Hdac3),这是染色体重塑中的关键酶.
- Ncor1对生命至关重要,因此其在成人生理学和Hdac3调节中的具体作用尚不清楚.
研究的目的:
- 在成年哺乳动物中研究Ncor1-Hdac3相互作用的生理重要性.
- 确定破坏这种相互作用对昼夜行为和代谢调节的影响.
主要方法:
- 在小鼠中Ncor1-Hdac3相互作用的遗传破坏.
- 对昼夜行为模式的分析.
- 评估代谢参数,包括身体组成,胰岛素敏感性和能量消耗.
- 时钟和代谢基因的基因表达分析.
主要成果:
- 在小鼠中,Ncor1-Hdac3复合物的特定遗传干扰导致异常的时钟基因调节和异常的昼夜行为.
- 被破坏Ncor1-Hdac3相互作用的小鼠表现出体重减轻,胰岛素敏感性增加和能量消耗增加.
- 功能性Ncor1-Hdac3复合物的丧失改变了代谢基因的振荡模式,而不是导致触媒基因持续增加.
结论:
- Ncor1-Hdac3复合体对于昼夜节律和代谢生理学的表观遗传调节至关重要.
- 循环节调节新陈代谢对于维持正常的能量平衡至关重要.
- 通过Ncor1介导的Hdac3激活代表了整合昼夜和代谢途径的节点点.
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