PT  - JOURNAL ARTICLE
AU  - Menon, Debashish U.
AU  - Murcia, Noel
AU  - Magnuson, Terry
TI  - ARID1A governs the silencing of sex-linked transcription during male meiosis in the mouse
AID  - 10.1101/2023.05.25.542290
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.05.25.542290
4099  - http://biorxiv.org/content/early/2023/05/25/2023.05.25.542290.short
4100  - http://biorxiv.org/content/early/2023/05/25/2023.05.25.542290.full
AB  - We present evidence implicating the BAF (BRG1/BRM Associated Factor) chromatin remodeler in meiotic sex chromosome inactivation (MSCI). By immunofluorescence (IF), the putative BAF DNA binding subunit, ARID1A (AT-rich Interaction Domain 1a), appeared enriched on the male sex chromosomes during diplonema of meiosis I. The germ cell-specific depletion of ARID1A resulted in a pachynema arrest and failure to repress sex-linked genes indicating a defective MSCI. Consistent with this defect, mutant sex chromosomes displayed an abnormal presence of elongating RNA polymerase II coupled with an overall increase in chromatin accessibility detectable by ATAC-seq. By investigating potential mechanisms underlying these anomalies, we identified a role for ARID1A in promoting the preferential enrichment of the histone variant, H3.3, on the sex chromosomes, a known hallmark of MSCI. Without ARID1A, the sex chromosomes appeared depleted of H3.3 at levels resembling autosomes. Higher resolution analyses by CUT&RUN revealed dramatic shifts in sex-linked H3.3 associations from discrete intergenic sites and broader gene-body domains to promoters in response to the loss of ARID1A. Several sex-linked sites displayed ectopic H3.3 occupancy that does not co-localize with DMC1 (DNA Meiotic Recombinase 1). This observation suggests a requirement for ARID1A in DMC1 localization to the asynapsed sex chromatids. We conclude that ARID1A-directed H3.3 localization influences sex chromosome gene regulation and DNA repair during meiosis I.Competing Interest StatementThe authors have declared no competing interest.