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| Status |
Public on Nov 01, 2018 |
| Title |
Setdb1 is essential for meiotic sex chromosome inactivation in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Meiotic synapsis and recombination ensure correct homologous segregation and genetic diversity. Asynapsed homologues are transcriptionally inactivated by meiotic silencing, which serves a surveillance function and in males drives meiotic sex chromosome inactivation. Silencing depends on the DNA damage response (DDR) network, but how DDR proteins engage repressive chromatin marks is unknown. We identify the histone H3-lysine-9 methyltransferase SETDB1 as the bridge linking the DDR to silencing in male mice. At the onset of silencing, X-chromosome H3K9 trimethylation (H3K9me3) enrichment is downstream of DDR factors. Without Setdb1, the X chromosome accrues DDR proteins but not H3K9me3. Consequently, sex chromosome remodelling and silencing fails, causing germ cell apoptosis. Our data implicate TRIM28 in linking the DDR to SETDB1, and uncover additional factors with putative meiotic XY-silencing functions. Furthermore, we show that SETDB1 imposes timely expression of meiotic and post-meiotic genes. Setdb1 thus unites the DDR network, asynapsis and meiotic chromosome silencing.
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| Overall design |
Transcriptome and H3K9me3 ChIP-seq profiles in Setdb1 wildtype and cKO pachytene spermatocytes
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| Contributor(s) |
Hirota T, Blakeley P, Sangrithi MN, Mahadevaiah SK, Encheva V, Snijders AP, ElInati E, Ojarikre OA, de Rooij DG, Niakan KK, Turner JM |
| Citation(s) |
30393076 |
| Submission date |
Dec 04, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Takayuki Hirota |
| Organization name |
The Francis Crick Institute
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| Lab |
Sex Chromosome Biology Laboratory
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| Street address |
1 Midland Road
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| City |
London |
| ZIP/Postal code |
NW1 1AT |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA420999 |
| SRA |
SRP126092 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107671_H3K9me3_WT_over_KO.bw |
139.0 Mb |
(ftp)(http) |
BW |
| GSE107671_abundance.xlsx |
4.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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