Work

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

Year: 2021
Type: article
Abstract: BRG1, a catalytic subunit of the mammalian SWI/SNF nucleosome remodeler is essential for male meiosis 1 . In addition to BRG1, multiple subunits (~10-14) some of which are mutually exclusive, constitute biochemically distinct SWI/SNF subcomplexes, whose functions in gametogenesis remain unknown. Here, we identify a role for the PBAF (Polybromo - B rg1 A ssociated F actor) complex in the regulation of meiotic cell division. The germ cell-specific depletion of PBAF specific subunit, ARID2 resulted in a metaphase-I arrest. Arid2 cKO metaphase-I spermatocytes displayed defects in chromosome organization and spindle assembly. Additionally, mutant centromeres were devoid of Polo-like kinase1 (PLK1), a known regulator of the spindle assembly checkpoint (SAC) 2 . The loss of PLK1 coincided with an abnormal chromosome-wide expansion of centromeric chromatin modifications such as Histone H3 threonine3 phosphorylation (H3T3P) and Histone H2A threonine120 phosphorylation (H2AT120P) that are critical for chromosome segregation 3,4 . Consistent with the known role of these histone modifications in chromosome passenger complex (CPC) recruitment, Arid2 cKO metaphase-I chromosomes display defects in CPC association. We propose that ARID2 facilitates metaphase-I exit by regulating spindle assembly and centromeric chromatin.
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $5,560
OpenAlex ID: W3214668460
FWCI: 3.982
Cites: 100
Cited by: 29
Related to: 10