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多梳抑制复合物 1:从胚胎到成年阶段神经发生的调控因子。

Polycomb repressive complex 1: Regulators of neurogenesis from embryonic to adult stage.

机构信息

Department of Biological Sciences, Sunandan Divatia School of Science (SDSOS), Narsee Monjee Institute of Management Studies (NMIMS) deemed-to-be University, Mumbai, India.

Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis International University (SIU), Pune, India.

出版信息

J Cell Physiol. 2020 May;235(5):4031-4045. doi: 10.1002/jcp.29299. Epub 2019 Oct 14.

DOI:10.1002/jcp.29299
PMID:31608994
Abstract

Development of vertebrate nervous system is a complex process which involves differential gene expression and disruptions in this process or in the mature brain, may lead to neurological disorders and diseases. Extensive work that spanned several decades using rodent models and recent work on stem cells have helped uncover the intricate process of neuronal differentiation and maturation. There are various morphological changes, genetic and epigenetic modifications which occur during normal mammalian neural development, one of the chromatin modifications that controls vital gene expression are the posttranslational modifications on histone proteins, that controls accessibility of translational machinery. Among the histone modifiers, polycomb group proteins (PcGs), such as Ezh2, Eed and Suz12 form large protein complexes-polycomb repressive complex 2 (PRC2); while Ring1b and Bmi1 proteins form core of PRC1 along with accessory proteins such as Cbx, Hph, Rybp and Pcgfs catalyse histone modifications such as H3K27me3 and H2AK119ub1. PRC1 proteins are known to play critical role in X chromosome inactivation in females but they also repress the expression of key developmental genes and tightly regulate the mammalian neuronal development. In this review we have discussed the signalling pathways, morphogens and nuclear factors that initiate, regulate and maintain cells of the nervous system. Further, we have extensively reviewed the recent literature on the role of Ring1b and Bmi1 in mammalian neuronal development and differentiation; as well as highlighted questions that are still unanswered.

摘要

脊椎动物神经系统的发育是一个复杂的过程,涉及差异基因表达,而这个过程或成熟大脑中的任何中断,都可能导致神经紊乱和疾病。几十年来,使用啮齿动物模型和最近的干细胞研究已经进行了广泛的工作,这些工作帮助揭示了神经元分化和成熟的复杂过程。在正常哺乳动物神经发育过程中会发生各种形态变化、遗传和表观遗传修饰,其中一种控制重要基因表达的染色质修饰是组蛋白的翻译后修饰,它控制着翻译机制的可及性。在组蛋白修饰物中,多梳蛋白(PcG)家族蛋白,如 Ezh2、Eed 和 Suz12 形成大的蛋白复合物——多梳抑制复合物 2(PRC2);而 Ring1b 和 Bmi1 蛋白与辅助蛋白(如 Cbx、Hph、Rybp 和 Pcgfs)一起形成 PRC1 的核心,催化组蛋白修饰,如 H3K27me3 和 H2AK119ub1。PRC1 蛋白已知在女性的 X 染色体失活中发挥关键作用,但它们也抑制关键发育基因的表达,并严格调节哺乳动物神经元发育。在这篇综述中,我们讨论了启动、调节和维持神经系统细胞的信号通路、形态发生素和核因子。此外,我们还广泛回顾了关于 Ring1b 和 Bmi1 在哺乳动物神经元发育和分化中的作用的最新文献,并强调了仍未解答的问题。

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