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

• Published in: Nature communications Vol. 12; no. 1; pp. 6581 - 19
• Main Authors: Menon, Debashish U., Kirsanov, Oleksandr, Geyer, Christopher B., Magnuson, Terry
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/44; 14; 14/1; 38; 38/15; 38/23; 38/39; 38/77; 45; 631/136/2434/1822; 631/208/176/2016; 631/80/641/1633; Animals; Assembly; BRG1 protein; Cell Cycle Proteins - metabolism; Cell division; Centromere - metabolism; Centromeres; Chromatin; Chromatin Assembly and Disassembly; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Chromosomes; DNA Helicases - metabolism; Gametocytes; Gene expression; Gene Silencing; Genes; Histone H2A; Histone H3; Histones; Histones - metabolism; Humanities and Social Sciences; Male; Males; Mammals; Mammals - genetics; Meiosis; Metaphase; Mice; Mice, Knockout; multidisciplinary; Nuclear division; Nuclear Proteins - metabolism; Phosphorylation; Polo-Like Kinase 1; Promoter Regions, Genetic; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Science; Science (multidisciplinary); Spermatocytes; Spermatocytes - metabolism; Spermatogenesis; Spermatogenesis - genetics; Spindles; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptome
• ISSN: 2041-1723; 2041-1723
• 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 cKO 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 ( Pp1 γ), 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. The mammalian SWI/SNF nucleosome remodeler is required for spermatogenesis. Here, the authors show that PBAF is essential for meiotic cell division in males and required to activate the expression of critical genes involved in spindle assembly and nuclear division in spermatocytes.