|
| 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)
|
|
| This SubSeries is part of SuperSeries: |
| GSE225612 |
ARID1A governs silencing of sex-linked transcription during male meiosis in the mouse. |
|
| Relations |
| BioProject |
PRJNA936619 |
Less...
More...