Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males

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作者
Debashish U. Menon
Oleksandr Kirsanov
Christopher B. Geyer
Terry Magnuson
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[1] The University of North Carolina at Chapel Hill,Department of Genetics, and Lineberger Comprehensive Cancer Center
[2] East Carolina University,Department of Anatomy & Cell Biology at the Brody School of Medicine
[3] East Carolina Diabetes and Obesity Institute,undefined
[4] East Carolina University,undefined
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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. Arid2cKO 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.
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