SWI/SNF家族染色体重塑复合物的模块化组织和组装
Nazar Mashtalir1, Andrew R D'Avino1, Brittany C Michel2
1Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell
|October 23, 2018
概括
哺乳动物SWI/SNF (mSWI/SNF) 复合体对于基因组调节至关重要,并且与疾病有关. 这项研究揭示了它们的模块化组织和组装途径,有助于未来的结构和功能研究.
科学领域:
- 分子生物学
- 基因组学
- 生物化学
背景情况:
- 哺乳动物SWI/SNF (mSWI/SNF) 复合体是ATP依赖的染色质重塑剂,对基因组调节至关重要.
- mSWI/SNF复合物的干扰与人类的癌症和发育障碍有关.
- 这些复合体的模块化组织和组装途径在很大程度上仍然没有特征.
研究的目的:
- 阐明三大类mSWI/SNF复合体的架构和组装路径:BAF,PBAF和ncBAF.
- 定义单个子单位在复杂形成和稳定中的作用.
- 在复杂结构和子单元相互作用的背景下绘制与疾病相关的突变.
主要方法:
- 来自哺乳动物和虫细胞的内源mSWI/SNF复合物的亲和性净化.
- 交联质谱 (CX-MS) 用于确定子单元的近距离和相互作用.
- 位点定向突变,以评估复杂组装和稳定性所需的子单元.
主要成果:
- 在mSWI/SNF复合体内确定了三个不同的,在进化上保存的模块化单元.
- 在复杂的组装过程中对这些模块的顺序结合的描述.
- 将与疾病相关的突变映射到特定的子单位和拓区域.
结论:
- 这项研究为了解mSWI/SNF复杂架构和组装提供了全面的框架.
- 这种知识对于解读癌症和发育障碍突变的功能后果至关重要.
- 这些发现为未来对这些重要染色体调节剂的结构和功能研究铺平了道路.
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