Chmykhalo Victor K, Deev Roman V, Tokarev Artemiy T, Polunina Yulia A, Xue Lei, Shidlovskii Yulii V
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilova St, Moscow, 119334, Russia.
School of Life Science and Technology, The First Rehabilitation Hospital of Shanghai, Tongji University, Shanghai, China.
Mol Neurobiol. 2025 Feb;62(2):1536-1557. doi: 10.1007/s12035-024-04355-6. Epub 2024 Jul 13.
SWI/SNF protein complexes are evolutionarily conserved epigenetic regulators described in all eukaryotes. In metameric animals, the complexes are involved in all processes occurring in the nervous system, from neurogenesis to higher brain functions. On the one hand, the range of roles is wide because the SWI/SNF complexes act universally by mobilizing the nucleosomes in a chromatin template at multiple loci throughout the genome. On the other hand, the complexes mediate the action of multiple signaling pathways that control most aspects of neural tissue development and function. The issues are discussed to provide insight into the molecular basis of the multifaceted role of SWI/SNFs in cell cycle regulation, DNA repair, activation of immediate-early genes, neurogenesis, and brain and connectome formation. An overview is additionally provided for the molecular basis of nervous system pathologies associated with the SWI/SNF complexes and their contribution to neuroinflammation and neurodegeneration. Finally, we discuss the idea that SWI/SNFs act as an integration platform to connect multiple signaling and genetic programs.
SWI/SNF蛋白复合物是在所有真核生物中都有描述的进化保守的表观遗传调节因子。在分节动物中,这些复合物参与神经系统中发生的所有过程,从神经发生到高级脑功能。一方面,其作用范围很广,因为SWI/SNF复合物通过在整个基因组的多个位点上动员染色质模板中的核小体而普遍发挥作用。另一方面,这些复合物介导多种信号通路的作用,这些信号通路控制神经组织发育和功能的大多数方面。本文将讨论这些问题,以深入了解SWI/SNF在细胞周期调控、DNA修复、即早基因激活、神经发生以及脑和连接组形成中的多方面作用的分子基础。此外,还将概述与SWI/SNF复合物相关的神经系统病理学的分子基础及其对神经炎症和神经退行性变的影响。最后,我们讨论SWI/SNF作为连接多个信号和遗传程序的整合平台的观点。