Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Mol Cell Neurosci. 2018 Mar;87:55-64. doi: 10.1016/j.mcn.2017.10.008. Epub 2017 Dec 15.
The mammalian ISWI (Imitation Switch) genes SMARCA1 and SMARCA5 encode the ATP-dependent chromatin remodeling proteins SNF2L and SNF2H. The ISWI proteins interact with BAZ (bromodomain adjacent to PHD zinc finger) domain containing proteins to generate eight distinct remodeling complexes. ISWI complex-mediated nucleosome positioning within genes and gene regulatory elements is proving important for the transition from a committed progenitor state to a differentiated cell state. Genetic studies have implicated the involvement of many ATP-dependent chromatin remodeling proteins in neurodevelopmental disorders (NDDs), including SMARCA1. Here we review the characterization of mice inactivated for ISWI and their interacting proteins, as it pertains to brain development and disease. A better understanding of chromatin dynamics during neural development is a prerequisite to understanding disease pathologies and the development of therapeutics for these complex disorders.
哺乳动物的 ISWI（模仿开关）基因 SMARCA1 和 SMARCA5 编码 ATP 依赖性染色质重塑蛋白 SNF2L 和 SNF2H。ISWI 蛋白与含有 BAZ（紧邻 PHF 锌指的溴结构域）结构域的蛋白质相互作用，产生八个不同的重塑复合物。ISWI 复合物介导的核小体在基因和基因调控元件内的定位对于从定向祖细胞状态向分化细胞状态的转变很重要。遗传研究表明，许多 ATP 依赖性染色质重塑蛋白参与神经发育障碍（NDD），包括 SMARCA1。在这里，我们回顾了 ISWI 及其相互作用蛋白失活的小鼠的特征，以及它们与大脑发育和疾病的关系。更好地了解神经发育过程中的染色质动态是理解疾病病理学和为这些复杂疾病开发治疗方法的前提。
