| First Author | Eckersley-Maslin MA | Year | 2020 |
| Journal | Nat Struct Mol Biol | Volume | 27 |
| Issue | 8 | Pages | 696-705 |
| PubMed ID | 32572255 | Mgi Jnum | J:297729 |
| Mgi Id | MGI:6479195 | Doi | 10.1038/s41594-020-0443-3 |
| Citation | Eckersley-Maslin MA, et al. (2020) Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment. Nat Struct Mol Biol 27(8):696-705 |
| abstractText | How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double knockout mouse embryonic stem cells fail to exit pluripotency and differentiate efficiently. DPPA2/4 bind both H3K4me3-marked and bivalent gene promoters and associate with COMPASS- and Polycomb-bound chromatin. Comparing knockout and inducible knockdown systems, we find that acute depletion of DPPA2/4 results in rapid loss of H3K4me3 from key bivalent genes, while H3K27me3 is initially more stable but lost following extended culture. Consequently, upon DPPA2/4 depletion, these promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel epigenetic priming mechanism at developmental promoters, poising them for future lineage-specific activation. |
