The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders
The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders
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DOI：
10.1016/j.mcn.2017.10.008
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发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
Picketts, David J.
中科院分区：
文献类型：
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作者：
Goodwin, Laura R.;Picketts, David J.
哺乳动物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（毗邻PHD锌指的溴结构域）结构域的蛋白相互作用，产生8种不同的重塑复合物。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固定祖细胞状态过渡到分化细胞状态非常重要。遗传学研究表明，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失活小鼠及其相互作用蛋白的特征，因为它与大脑发育和疾病有关。更好地理解神经发育过程中的染色质动力学是理解疾病病理和开发这些复杂疾病的治疗方法的先决条件。
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.