{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Eckersley-Maslin MA"],"funding":["Cancer Research UK","Medical Research Council","Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["696-705"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7614975"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(8)"],"pubmed_abstract":["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."],"journal":["Nature structural & molecular biology"],"pubmed_title":["Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment."],"pmcid":["PMC7614975"],"funding_grant_id":["BB/K010867/1","095645/Z/11/Z","MR/M008975/1","215912/Z/19/Z","24453","215912","BBS/E/B/000C0422","22310","BBS/E/B/000C0421","C9545/A29580","BBS/E/B/0000H334","BB/T009713/1"],"pubmed_authors":["Krueger C","Reik W","Ito Y","Franklin VNR","D'Santos CS","Blotenburg M","Narita M","Eckersley-Maslin MA","Parry A"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Aug","modification":"2025-04-04T02:26:25.579Z","creation":"2025-04-04T02:26:25.579Z"},"accession":"S-EPMC7614975","cross_references":{"pubmed":["32572255"],"doi":["10.1038/s41594-020-0443-3"]}}