Show simple item record

dc.contributor.authorBleckwehl, Tore
dc.contributor.authorCrispatzu, Giuliano
dc.contributor.authorSchaaf, Kaitlin
dc.contributor.authorRespuela, Patricia
dc.contributor.authorBartusel, Michaela
dc.contributor.authorBenson, Laura
dc.contributor.authorClark, Stephen J
dc.contributor.authorDorighi, Kristel M
dc.contributor.authorBarral, Antonio
dc.contributor.authorLaugsch, Magdalena
dc.contributor.authorvan IJcken, Wilfred FJ
dc.contributor.authorManzanares, Miguel
dc.contributor.authorWysocka, Joanna
dc.contributor.authorReik, Wolf
dc.contributor.authorRada-Iglesias, Álvaro
dc.date.accessioned2021-11-03T01:40:23Z
dc.date.available2021-11-03T01:40:23Z
dc.date.issued2021-10-01
dc.identifier.issn2041-1723
dc.identifier.otherPMC8486853
dc.identifier.other34599190
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330215
dc.descriptionFunder: Studienstiftung des Deutschen Volkes
dc.description.abstractGermline specification in mammals occurs through an inductive process whereby competent cells in the post-implantation epiblast differentiate into primordial germ cells (PGC). The intrinsic factors that endow epiblast cells with the competence to respond to germline inductive signals remain unknown. Single-cell RNA sequencing across multiple stages of an in vitro PGC-like cells (PGCLC) differentiation system shows that PGCLC genes initially expressed in the naïve pluripotent stage become homogeneously dismantled in germline competent epiblast like-cells (EpiLC). In contrast, the decommissioning of enhancers associated with these germline genes is incomplete. Namely, a subset of these enhancers partly retain H3K4me1, accumulate less heterochromatic marks and remain accessible and responsive to transcriptional activators. Subsequently, as in vitro germline competence is lost, these enhancers get further decommissioned and lose their responsiveness to transcriptional activators. Importantly, using H3K4me1-deficient cells, we show that the loss of this histone modification reduces the germline competence of EpiLC and decreases PGCLC differentiation efficiency. Our work suggests that, although H3K4me1 might not be essential for enhancer function, it can facilitate the (re)activation of enhancers and the establishment of gene expression programs during specific developmental transitions.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.titleEnhancer-associated H3K4 methylation safeguards in vitro germline competence.
dc.typeArticle
dc.date.updated2021-11-03T01:40:22Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.77657
dcterms.dateAccepted2021-09-16
rioxxterms.versionofrecord10.1038/s41467-021-26065-6
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBleckwehl, Tore [0000-0003-1116-0512]
dc.contributor.orcidCrispatzu, Giuliano [0000-0001-8041-2125]
dc.contributor.orcidBartusel, Michaela [0000-0003-1008-1951]
dc.contributor.orcidBenson, Laura [0000-0002-7239-6126]
dc.contributor.orcidClark, Stephen J [0000-0002-6183-491X]
dc.contributor.orcidvan IJcken, Wilfred FJ [0000-0002-0421-8301]
dc.contributor.orcidManzanares, Miguel [0000-0003-4849-2836]
dc.contributor.orcidWysocka, Joanna [0000-0002-6909-6544]
dc.contributor.orcidReik, Wolf [0000-0003-0216-9881]
dc.contributor.orcidRada-Iglesias, Álvaro [0000-0001-7137-1341]
dc.identifier.eissn2041-1723
pubs.funder-project-idEuropean Research Council (862022)
cam.issuedOnline2021-10


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International