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染色质重塑复合物NuRD在神经发育及神经发育障碍中的作用

Chromatin Remodeling Complex NuRD in Neurodevelopment and Neurodevelopmental Disorders.

作者信息

Hoffmann Anke, Spengler Dietmar

机构信息

Epigenomics of Early Life, Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.

出版信息

Front Genet. 2019 Jul 24;10:682. doi: 10.3389/fgene.2019.00682. eCollection 2019.

Abstract

The nucleosome remodeling and deacetylase (NuRD) complex presents one of the major chromatin remodeling complexes in mammalian cells. Here, we discuss current evidence for NuRD's role as an important epigenetic regulator of gene expression in neural stem cell (NSC) and neural progenitor cell (NPC) fate decisions in brain development. With the formation of the cerebellar and cerebral cortex, NuRD facilitates experience-dependent cerebellar plasticity and regulates additionally cerebral subtype specification and connectivity in postmitotic neurons. Consistent with these properties, genetic variation in NuRD's subunits emerges as important risk factor in common polygenic forms of neurodevelopmental disorders (NDDs) and neurodevelopment-related psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BD). Overall, these findings highlight the critical role of NuRD in chromatin regulation in brain development and in mental health and disease.

摘要

核小体重塑与去乙酰化酶(NuRD)复合体是哺乳动物细胞中主要的染色质重塑复合体之一。在此,我们讨论目前关于NuRD在脑发育过程中作为神经干细胞(NSC)和神经祖细胞(NPC)命运决定中基因表达的重要表观遗传调节因子作用的证据。随着小脑和大脑皮质的形成,NuRD促进依赖经验的小脑可塑性,并额外调节有丝分裂后神经元中的大脑亚型特化和连接性。与这些特性一致,NuRD亚基的基因变异成为常见多基因形式的神经发育障碍(NDDs)以及神经发育相关精神疾病如精神分裂症(SCZ)和双相情感障碍(BD)的重要危险因素。总体而言,这些发现突出了NuRD在脑发育以及心理健康和疾病的染色质调节中的关键作用。

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