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| Status |
Public on Oct 05, 2022 |
| Title |
Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Meiotic sex chromosome inactivation (MSCI) is an essential process in the male germline. While genetic experiments have established that the DNA damage response (DDR) pathway directs MSCI, due to limitations to the experimental systems available, mechanisms underlying MSCI remain largely unknown. Here we establish a system to study MSCI ex vivo, based on a short-term culture method, and demonstrate that active DDR signaling is required both to initiate and maintain MSCI via a dynamic and reversible process. DDR-directed MSCI follows two layers of modifications: active DDR-dependent reversible processes and irreversible histone post-translational modifications. Further, the DDR initiates MSCI independent of the downstream repressive histone mark H3K9 trimethylation (H3K9me3), thereby demonstrating that active DDR signaling is the primary mechanism of silencing in MSCI. By unveiling the dynamic nature of MSCI, and its governance by active DDR signals, our study highlights the sex chromosomes as an active signaling hub in meiosis.
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| Overall design |
The isolated pachytene spermatocytes were cultured with DMSO or 10 µM AZ20 for 24 h at 34 C at 5% CO2.RNA-seq analysis using cultured spermatocytes for 24 h.
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| Contributor(s) |
Abe H, Munakata Y, Namekawa S |
| Citation(s) |
36443288 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 GM098605 |
DNA Damage Response Pathways in Meiotic Sex Chromosome Inactivation |
CHILDREN'S HOSPITAL MEDICAL CENTER |
Satoshi Namekawa |
| R35 GM141085 |
Epigenetic gene regulation in the germline |
UNIVERSITY OF CALIFORNIA DAVIS |
Satoshi Namekawa |
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| Submission date |
Aug 17, 2022 |
| Last update date |
Dec 15, 2022 |
| Contact name |
Satoshi H Namekawa |
| E-mail(s) |
snamekawa@ucdavis.edu
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| Organization name |
University of California, Davis
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| Department |
Department of Molecular and Cellular Biology
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| Street address |
One Shields Avenue
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA870643 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211519_PS_Ctrl_and_AZ_TPMs.txt.gz |
451.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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