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| Status |
Public on Mar 07, 2018 |
| Title |
Epigenetic reprogramming enables the primordial germ cell-to-gonocyte transition (WGBS) |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Gametes are highly specialised cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mouse, germ cells are first specified in the developing embryo as primordial germ cells (PGCs) starting around embryonic day (E) 6.25. Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming at E10.5/E11.5, including genome-wide loss of 5-methylcytosine (5mC). The underlying molecular mechanisms of this process have remained enigmatic leading to our inability to recapitulate this step of germline development in vitro. Using an integrative approach, we show that this complex reprogramming process involves the coordinated interplay between promoter sequence characteristics, DNA (de)methylation, Polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of Tet1 to enable the activation of a critical set of germline reprogramming responsive (GRR) genes involved in gamete generation and meiosis. Our results also unexpectedly reveal a role for Tet1 in safeguarding but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will be instructive towards recapitulating complete gametogenesis in vitro.
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| Overall design |
Whole genome bisulphite sequencing of PGCs between E10.5 and E12.5; male and female samples were treated separately following the initiation of sex specification (i.e. from E12.5)
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| |
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| Contributor(s) |
Hill P, Hajkova P, Sun Z, Dharmalingam G |
| Citation(s) |
29513657 |
| |
| Submission date |
Jan 19, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter Hill |
| E-mail(s) |
peter.hill1@imperial.ac.uk
|
| Organization name |
Imperial College London
|
| Street address |
Kensington
|
| City |
London |
| ZIP/Postal code |
SW7 2AZ |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE76973 |
Epigenetic reprogramming enables the primordial germ cell-to-gonocyte transition |
|
| Relations |
| BioProject |
PRJNA309357 |
| SRA |
SRP068730 |
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