Snf5缺失诱导异常SWI/SNF复合物的形成。
Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex.
作者信息
Sen Payel, Luo Jie, Hada Arjan, Hailu Solomon G, Dechassa Mekonnen Lemma, Persinger Jim, Brahma Sandipan, Paul Somnath, Ranish Jeff, Bartholomew Blaine
机构信息
Department of Biochemistry and Molecular Biology, Southern Illinois University, Carbondale, IL 62901, USA.
Institute for Systems Biology, Seattle, WA 98109, USA.
出版信息
Cell Rep. 2017 Feb 28;18(9):2135-2147. doi: 10.1016/j.celrep.2017.02.017.
The SWI/SNF chromatin remodeling complex is highly conserved from yeast to human, and aberrant SWI/SNF complexes contribute to human disease. The Snf5/SMARCB1/INI1 subunit of SWI/SNF is a tumor suppressor frequently lost in pediatric rhabdoid cancers. We examined the effects of Snf5 loss on the composition, nucleosome binding, recruitment, and remodeling activities of yeast SWI/SNF. The Snf5 subunit is shown by crosslinking-mass spectrometry (CX-MS) and subunit deletion analysis to interact with the ATPase domain of Snf2 and to form a submodule consisting of Snf5, Swp82, and Taf14. Snf5 promotes binding of the Snf2 ATPase domain to nucleosomal DNA and enhances the catalytic and nucleosome remodeling activities of SWI/SNF. Snf5 is also required for SWI/SNF recruitment by acidic transcription factors. RNA-seq analysis suggests that both the recruitment and remodeling functions of Snf5 are required in vivo for SWI/SNF regulation of gene expression. Thus, loss of SNF5 alters the structure and function of SWI/SNF.
SWI/SNF染色质重塑复合体从酵母到人类都高度保守，异常的SWI/SNF复合体与人类疾病有关。SWI/SNF的Snf5/SMARCB1/INI1亚基是一种肿瘤抑制因子，在儿童横纹肌肉瘤中经常缺失。我们研究了Snf5缺失对酵母SWI/SNF的组成、核小体结合、募集和重塑活性的影响。交联质谱（CX-MS）和亚基缺失分析表明，Snf5亚基与Snf2的ATP酶结构域相互作用，并形成一个由Snf5、Swp82和Taf14组成的子模块。Snf5促进Snf2 ATP酶结构域与核小体DNA的结合，并增强SWI/SNF的催化和核小体重塑活性。酸性转录因子招募SWI/SNF也需要Snf5。RNA测序分析表明，Snf5的募集和重塑功能在体内都是SWI/SNF调节基因表达所必需的。因此，SNF5的缺失会改变SWI/SNF的结构和功能。
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