 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 25, 2019 |
| Title |
ANKRD31 anchors meiotic double-strand break formation as a direct partner of REC114 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Homologous recombination initiated by double-strand breaks (DSBs) is crucial for chromosome pairing and segregation during meiosis. Here we unveil mouse ANKRD31 as a lynchpin controlling DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to X and Y pseudoautosomal regions (PAR). They also have delayed and fewer recombination sites but, paradoxically, more total DSBs, indicating DSB dysregulation. Unrepaired DSBs and pairing failures—stochastic on autosomes, nearly absolute on X and Y—cause meiotic arrest and male sterility, while Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines direct ANKRD31–REC114 molecular contacts and reveals a surprising pleckstrin homology domain in REC114. In vivo, ANKRD31 recruits REC114 to the PAR and elsewhere. Our findings inform a model that ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, promoting efficient and timely DSB formation but also suppressing formation of clustered DSBs.
|
| |
|
| Overall design |
For ssDNA sequencing: Three samples of juvenile mice from same breeding colony (Ankrd31 knocknout, heterozygote, and wild type control); one sample of Ankrd31 knockout adult; one sample of wild type adult; two samples of wild type adult (one of which is a control using an irrelevant-antibody); and one sample from Prdm9 knockout adult. For H3K4me3 ChIPseq: two biological replicates each of wild type and Ankrd31 knockout.
|
| |
|
| Contributor(s) |
Boekhout M, Karasu ME, Wang J, Acquaviva L, Pratto F, Brick K, Eng DY, Camerini-Otero RD, Patel DJ, Keeney S |
| Citation(s) |
31003867 |
| Submission date |
Aug 22, 2018 |
| Last update date |
Dec 25, 2019 |
| Contact name |
Kevin Brick |
| E-mail(s) |
brickkm@mail.nih.gov, kevbrick@gmail.com, brickkm@niddk.nih.gov
|
| Organization name |
NIDDK
|
| Department |
GBB
|
| Street address |
5/205 Memorial Drive
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (11)
|
|
| Relations |
| BioProject |
PRJNA487273 |
| SRA |
SRP158600 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118913_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BED, BIGWIG) |
| GSE118913_dataTable_hotspots.tab.gz |
1.3 Mb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...