Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA.
Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Int J Mol Sci. 2023 Jul 9;24(14):11256. doi: 10.3390/ijms241411256.
Mammalian SWI/SNF (mSWI/SNF) complexes are ATP-dependent chromatin remodeling enzymes that are critical for normal cellular functions. mSWI/SNF enzymes are classified into three sub-families based on the presence of specific subunit proteins. The sub-families are Brm- or Brg1-associated factor (BAF), ncBAF (non-canonical BAF), and polybromo-associated BAF (PBAF). The biological roles for the different enzyme sub-families are poorly described. We knocked down the expression of genes encoding unique subunit proteins for each sub-family, , , and , which mark the BAF, ncBAF, and PBAF sub-families, respectively, and examined the requirement for each in myoblast differentiation. We found that Baf250A and the BAF complex were required to drive lineage-specific gene expression. KD of delayed differentiation. However, while the Baf250A-dependent gene expression profile included myogenic genes, the Brd9-dependent gene expression profile did not, suggesting Brd9 and the ncBAF complex indirectly contributed to differentiation. Baf180 was dispensable for myoblast differentiation. The results distinguish between the roles of the mSWI/SNF enzyme sub-families during myoblast differentiation.
哺乳动物 SWI/SNF(mSWI/SNF)复合物是依赖于 ATP 的染色质重塑酶,对于正常的细胞功能至关重要。mSWI/SNF 酶根据特定亚基蛋白的存在分为三个亚家族。亚家族为 Brm-或 Brg1 相关因子(BAF)、ncBAF(非典型 BAF)和多溴相关 BAF(PBAF)。不同酶亚家族的生物学作用描述甚少。我们敲低了每个亚家族独特的亚基蛋白编码基因的表达,分别标记 BAF、ncBAF 和 PBAF 亚家族,然后检查了它们在成肌细胞分化中的需求。我们发现 Baf250A 和 BAF 复合物是驱动谱系特异性基因表达所必需的。Baf250A 的 KD 延迟了分化。然而,虽然 Baf250A 依赖性基因表达谱包括肌生成基因,但 Brd9 依赖性基因表达谱却没有,这表明 Brd9 和 ncBAF 复合物间接促进了分化。Baf180 对于成肌细胞分化是可有可无的。这些结果区分了 mSWI/SNF 酶亚家族在成肌细胞分化过程中的作用。