Abstract
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.
Highlights
The mammalian SWI/SNF nucleosome remodeler is essential for spermatogenesis
We show that ARID2, a PBAF-specific subunit, is essential for reductional meiosis, a process by which parental genomes are halved at the end of MI
It is possible that these earlier stages are regulated by the BAF complex, while PBAF activity is restricted to late meiosis-I, given that ARID2 is detected from pachynema onwards
Summary
We identify a role for ARID2, a PBAF (Polybromo - Brg[1] Associated Factor)-specific subunit, in meiotic division. 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. Studies have identified at least three distinct subcomplexes, namely, BAF (Brahma/Brg[1] Associated Factor), PBAF (Polybromo-BAF), and ncBAF (noncanonical BAF)[8] The identities of these complexes are based on the presence of mutually exclusive subunits. ARID2 influences centrosome formation, the kinetochore association of the known regulator of anaphase onset Polo-like kinase[1] (PLK1), the centromeric targeting of Histone H3 threonine[3] phosphorylation (H3T3P)/histone H2A threonine[120] phosphorylation (H2AT120P), and localization of the chromosome passenger complex (CPC). The near absence of secondary spermatocytes and spermatids in the Arid2cKO testis indicates an essential role for ARID2 in meiotic cell division
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