组蛋白去乙酰化酶 3 对生理学的综合调控。
Integrative regulation of physiology by histone deacetylase 3.
机构信息
Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
出版信息
Nat Rev Mol Cell Biol. 2019 Feb;20(2):102-115. doi: 10.1038/s41580-018-0076-0.
Cell-type-specific gene expression is physiologically modulated by the binding of transcription factors to genomic enhancer sequences, to which chromatin modifiers such as histone deacetylases (HDACs) are recruited. Drugs that inhibit HDACs are in clinical use but lack specificity. HDAC3 is a stoichiometric component of nuclear receptor co-repressor complexes whose enzymatic activity depends on this interaction. HDAC3 is required for many aspects of mammalian development and physiology, for example, for controlling metabolism and circadian rhythms. In this Review, we discuss the mechanisms by which HDAC3 regulates cell type-specific enhancers, the structure of HDAC3 and its function as part of nuclear receptor co-repressors, its enzymatic activity and its post-translational modifications. We then discuss the plethora of tissue-specific physiological functions of HDAC3.
细胞类型特异性基因表达受转录因子与基因组增强子序列结合的生理调节，染色质修饰剂如组蛋白去乙酰化酶（HDACs）被招募到这些序列中。抑制 HDAC 的药物正在临床应用中，但缺乏特异性。HDAC3 是核受体共抑制复合物的化学计量组成部分，其酶活性依赖于这种相互作用。HDAC3 对于哺乳动物发育和生理的许多方面都是必需的，例如，控制代谢和昼夜节律。在这篇综述中，我们讨论了 HDAC3 调节细胞类型特异性增强子的机制、HDAC3 的结构及其作为核受体共抑制因子的功能、其酶活性及其翻译后修饰。然后，我们讨论了 HDAC3 众多的组织特异性生理功能。
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