Differential Contributions of mSWI/SNF Chromatin Remodeler Sub-Families to Myoblast Differentiation.
Differential Contributions of mSWI/SNF Chromatin Remodeler Sub-Families to Myoblast Differentiation.
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DOI：
10.3390/ijms241411256
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发表时间：
2023-07-09
影响因子：
5.6
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中科院分区：
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哺乳动物SWI/SNF（mSWI/SNF）复合物是ATP依赖性染色质重塑酶，其对正常细胞功能至关重要。基于特定亚基蛋白的存在，将mSWI/SNF酶分为三个亚家族。这些亚家族是Brm或Brg 1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得很少。我们敲低了每个亚家族Baf 250 A、Brd 9和Baf 180（分别标记BAF、ncBAF和PBAF亚家族）编码独特亚基蛋白的基因的表达，并检查了成肌细胞分化中对每个亚基蛋白的要求。我们发现Baf 250 A和BAF复合物是驱动谱系特异性基因表达所必需的。Brd 9的KD延迟分化。然而，虽然Baf 250 A依赖的基因表达谱包括生肌基因，但Brd 9依赖的基因表达谱没有，表明Brd 9和ncBAF复合物间接促进了分化。Baf 180在成肌细胞分化中起重要作用。结果区分了mSWI/SNF酶亚家族在成肌细胞分化过程中的作用。
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, Baf250A, Brd9, and Baf180, 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 Brd9 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.
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