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染色质重塑和核受体信号转导。

Chromatin remodeling and nuclear receptor signaling.

机构信息

Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

出版信息

Prog Mol Biol Transl Sci. 2009;87:193-234. doi: 10.1016/S1877-1173(09)87006-3. Epub 2009 Oct 7.

Abstract

Nuclear receptors (NRs) constitute a large family of ligand-dependent transcription factors that play key roles in development, differentiation, metabolism, and homeostasis. They participate in these processes by coordinating and regulating the expression of their target genes. The eukaryotic genome is packaged as chromatin and is generally inhibitory to the process of transcription. NRs overcome this barrier by recruiting two classes of chromatin remodelers, histone modifying enzymes and ATP-dependent chromatin remodelers. These remodelers alter chromatin structure at target gene promoters by posttranslational modification of histone tails and by disrupting DNA-histone interactions, respectively. In the presence of ligand, NRs promote transcription by recruiting remodeling enzymes that increase promoter accessibility to the basal transcription machinery. In the absence of ligand a subset of NRs recruit remodelers that establish and maintain a closed chromatin environment, to ensure efficient gene silencing. This chapter reviews the chromatin remodeling enzymes associated with NR gene control, with an emphasis on the mechanisms of NR-mediated repression.

摘要

核受体(NRs)是一大类配体依赖性转录因子家族,它们在发育、分化、代谢和内稳态中发挥关键作用。它们通过协调和调节其靶基因的表达来参与这些过程。真核基因组被包装为染色质,通常对转录过程具有抑制作用。NR 通过招募两类染色质重塑剂,组蛋白修饰酶和 ATP 依赖性染色质重塑剂,克服了这一障碍。这些重塑剂通过组蛋白尾部的翻译后修饰和破坏 DNA-组蛋白相互作用,分别改变靶基因启动子处的染色质结构。在配体存在的情况下,NR 通过招募增加启动子对基础转录机制可及性的重塑酶来促进转录。在没有配体的情况下,一部分 NR 招募重塑因子,建立和维持封闭的染色质环境,以确保有效的基因沉默。本章综述了与 NR 基因调控相关的染色质重塑酶,重点介绍了 NR 介导的抑制的机制。

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