Differential requirements for different subfamilies of the mammalian SWI/SNF chromatin remodeling enzymes in myoblast cell cycle progression and expression of the Pax7 regulator.
Differential requirements for different subfamilies of the mammalian SWI/SNF chromatin remodeling enzymes in myoblast cell cycle progression and expression of the Pax7 regulator.
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DOI：
10.1016/j.bbagrm.2022.194801
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Imbalzano AN
中科院分区：
文献类型：
--
作者：
Padilla-Benavides T;Olea-Flores M;Nshanji Y;Maung MT;Syed SA;Imbalzano AN
哺乳动物SWItch/Sucrose Non-Fermentable（mSWI/SNF）家族的ATP依赖性染色质重塑酶是基因表达的确定的共调节因子。mSWI/SNF复合物可以组装成三个主要的亚家族：BAF（BRG 1或BRM相关因子）、PBAF（含多溴BAF）或ncBAF（非典型BAF），它们的区别在于存在相互排斥的亚基。每个亚家族有助于特定细胞谱系的建立或功能的机制知之甚少。在这里，我们确定了BAF，ncBAF和PBAF复合物的贡献，成肌细胞增殖通过敲低（KD）的一个独特的亚基从每个复杂的。KD的BAF或ncBAF复合物独特的亚基降低成肌细胞增殖率，而KD的PBAF特异性亚基不影响增殖。来自增殖的KD成肌细胞的靶向Baf 250 A（BAF复合物）、Brd 9（ncBAF复合物）或Baf 180（PBAF复合物）的RNA-seq显示出有限数量的基因的错误调节。KD的Baf 250 A特异性地降低Pax 7的表达，这是成肌细胞增殖所必需的，伴随着Baf 250 A与Pax 7基因启动子的结合减少和受损的染色质重塑。虽然Brd 9也结合Pax 7启动子，表明ncBAF复合物的占用，没有变化，检测到Pax 7基因表达，Pax 7蛋白表达或染色质重塑在Pax 7启动子Brd 9 KD。这些数据表明，BAF亚家族的mSWI/SNF酶是特别需要的成肌细胞增殖通过调节Pax 7的表达。
The mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) family of ATP-dependent chromatin remodeling enzymes are established co-regulators of gene expression. mSWI/SNF complexes can be assembled into three major subfamilies: BAF (BRG1 or BRM-Associated Factor), PBAF (Polybromo containing BAF), or ncBAF (non-canonical BAF) that are distinguished by the presence of mutually exclusive subunits. The mechanisms by which each subfamily contributes to the establishment or function of specific cell lineages are poorly understood. Here, we determined the contributions of the BAF, ncBAF, and PBAF complexes to myoblast proliferation via knock down (KD) of a distinguishing subunits from each complex. KD of subunits unique to the BAF or the ncBAF complexes reduced myoblast proliferation rate, while KD of PBAF-specific subunits did not affect proliferation. RNA-seq from proliferating KD myoblasts targeting Baf250A (BAF complex), Brd9 (ncBAF complex), or Baf180 (PBAF complex) showed mis-regulation of a limited number of genes. KD of Baf250A specifically reduced the expression of Pax7, which is required for myoblast proliferation, concomitant with decreased binding of Baf250A to and impaired chromatin remodeling at the Pax7 gene promoter. Although Brd9 also bound to the Pax7 promoter, suggesting occupancy by the ncBAF complex, no changes were detected in Pax7 gene expression, Pax7 protein expression or chromatin remodeling at the Pax7 promoter upon Brd9 KD. The data indicate that the BAF subfamily of the mSWI/SNF enzymes is specifically required for myoblast proliferation via regulation of Pax7 expression.
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影响因子：
3.7
作者：
He L;Tian X;Zhang H;Hu T;Huang X;Zhang L;Wang Z;Zhou B
通讯作者：
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DOI：
10.1161/atvbaha.120.314955
发表时间：
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