Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7264, USA.
Department of Anatomy & Cell Biology at the Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Nat Commun. 2021 Nov 12;12(1):6581. doi: 10.1038/s41467-021-26828-1.
The mammalian SWI/SNF nucleosome remodeler is essential for spermatogenesis. Here, we identify a role for ARID2, a PBAF (Polybromo - Brg1 Associated Factor)-specific subunit, in meiotic division. Arid2 spermatocytes arrest at metaphase-I and are deficient in spindle assembly, kinetochore-associated Polo-like kinase1 (PLK1), and centromeric targeting of Histone H3 threonine3 phosphorylation (H3T3P) and Histone H2A threonine120 phosphorylation (H2AT120P). By determining ARID2 and BRG1 genomic associations, we show that PBAF localizes to centromeres and promoters of genes known to govern spindle assembly and nuclear division in spermatocytes. Consistent with gene ontology of target genes, we also identify a role for ARID2 in centrosome stability. Additionally, misexpression of genes such as Aurkc and Ppp1cc (Pp1γ), known to govern chromosome segregation, potentially compromises the function of the chromosome passenger complex (CPC) and deposition of H3T3P, respectively. Our data support a model where-in PBAF activates genes essential for meiotic cell division.
哺乳动物 SWI/SNF 核小体重塑酶是精子发生所必需的。在这里，我们确定了 ARID2（PBAF（多溴化 Brg1 相关因子）特异性亚基）在减数分裂中的有丝分裂作用。Arid2 精母细胞在中期 I 停滞，并且纺锤体组装、动粒相关 Polo 样激酶 1（PLK1）、组蛋白 H3 丝氨酸 3 磷酸化（H3T3P）和组蛋白 H2A 苏氨酸 120 磷酸化（H2AT120P）的中心体靶向缺失。通过确定 ARID2 和 BRG1 基因组关联，我们表明 PBAF 定位于中心体和已知调控精母细胞纺锤体组装和核分裂的基因启动子。与靶基因的基因本体论一致，我们还确定了 ARID2 在中心体稳定性中的作用。此外，已知调控染色体分离的基因如 Aurkc 和 Ppp1cc（Pp1γ）的异常表达，可能分别破坏染色体乘客复合物（CPC）的功能和 H3T3P 的沉积。我们的数据支持这样一种模型，即 PBAF 激活减数分裂细胞分裂所必需的基因。
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