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神经发育与疾病中的染色质重塑BAF(SWI/SNF)复合物

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.

作者信息

Sokpor Godwin, Xie Yuanbin, Rosenbusch Joachim, Tuoc Tran

机构信息

Institute of Neuroanatomy, University Medical Center, Georg-August-University GoettingenGoettingen, Germany.

DFG Center for Nanoscale Microscopy and Molecular Physiology of the BrainGoettingen, Germany.

出版信息

Front Mol Neurosci. 2017 Aug 3;10:243. doi: 10.3389/fnmol.2017.00243. eCollection 2017.

Abstract

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

摘要

ATP 依赖的 BRG1/BRM 相关因子(BAF)染色质重塑复合物通过控制染色质动态变化在调节基因表达中起关键作用。在过去十年中,越来越清楚的是,在哺乳动物神经发育过程中,神经祖细胞和有丝分裂后神经细胞中会形成由其亚基组合装配产生的不同个体发育阶段特异性 BAF 复合物。BAF 复合物的正常功能在神经发育中起关键作用,包括神经命运和功能的建立与维持。事实上,最近的人类外显子组测序和全基因组关联研究表明,BAF 复合物亚基的突变与多种神经发育障碍有关,如科芬-西里斯综合征、尼古拉德斯-巴拉伊特综合征、克莱夫斯特拉综合征谱系、先天性巨结肠、自闭症谱系障碍和精神分裂症。在本综述中,我们聚焦于神经发育过程中 BAF 复合物功能的最新见解,以及已知 BAF 亚基突变与某些神经发育障碍相关的可能机制基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f1/5540894/de90c6f40c45/fnmol-10-00243-g0001.jpg

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