|
| Status |
Public on May 28, 2020 |
| Title |
Dppa2/4 Counteract De Novo Methylation to Establish a Permissive Epigenome for Development [CRISPR] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Early mammalian development entails widespread epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate global and focal DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening. We identify key genes and regulatory pathways that drive developmental DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states during (re)programming phases. In their absence, developmental genes and evolutionary young LINE1 elements lose H3K4me3 and gain ectopic de novo DNA methylation. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory in pluripotent cells, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt a permissive epigenome for development by targeting H3K4me3 to counteract de novo methylation during (re)programming; a function that has been co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.
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| |
|
| Overall design |
Genome wide CRISPR knockout screening coupled with the eRGM cell lines to unbiasedly identify the gene networks that underpin DNA methylation remodeling
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| |
|
| Contributor(s) |
Gretarsson KH, Hackett JA |
| Citation(s) |
32572256 |
| |
| Submission date |
May 27, 2020 |
| Last update date |
Aug 27, 2020 |
| Contact name |
Kristjan Holm Gretarsson |
| E-mail(s) |
kristjan.gretarsson@embl.it
|
| Organization name |
EMBL Rome
|
| Lab |
Hackett Lab
|
| Street address |
Via Ercole Ramarini, 32
|
| City |
Monterotondo |
| State/province |
Roma |
| ZIP/Postal code |
00015 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE146863 |
Dppa2/4 Counteract De Novo Methylation to Establish a Permissive Epigenome for Development |
|
| Relations |
| BioProject |
PRJNA635360 |
| SRA |
SRP264932 |
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