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Series GSE225611 Query DataSets for GSE225611
Status Public on Feb 19, 2024
Title ARID1A governs silencing of sex-linked transcription during male meiosis in the mouse [ATAC-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design Changes in chromatin accessibility in response to the loss of ARID1A was determined by ATAC-seq. Cryopreserved aliquots of Arid1aWT and Arid1acKO pachytene spermatocytes purified by Sta-Put were processed in quadruplicate (100,000 cells/replicate) for ATAC-seq.
 
Contributor(s) Menon DU, Murcia N, Magnuson T
Citation(s) 39589400
Submission date Feb 19, 2023
Last update date Jan 28, 2025
Contact name Terry Magnuson
E-mail(s) trm4@med.unc.edu
Organization name University of North Carolina at Chapel Hill
Department Genetics
Lab Terry Magnuson
Street address 120 Mason Farm Road, Genetics Medicine Bldg.,
City Chapel hill
State/province NC
ZIP/Postal code 27599
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7051106 ARID1A_ATAC_WT1
GSM7051107 ARID1A_ATAC_WT2
GSM7051108 ARID1A_ATAC_WT3
This SubSeries is part of SuperSeries:
GSE225612 ARID1A governs silencing of sex-linked transcription during male meiosis in the mouse.
Relations
BioProject PRJNA936619

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE225611_AvgMUT_ATAC.bw 593.7 Mb (ftp)(http) BW
GSE225611_AvgWT_ATAC.bw 576.0 Mb (ftp)(http) BW
GSE225611_MUT_ATACblfilt_overlap.bed.gz 837.0 Kb (ftp)(http) BED
GSE225611_WT_ATACblfilt_overlap.bed.gz 535.6 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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