PRDM14 controls X-chromosomal and global epigenetic reprogramming of H3K27me3 in migrating mouse primordial germ cells

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  • dc.contributor.author Mallol, Anna
  • dc.contributor.author Guirola, Maria
  • dc.contributor.author Payer, Bernhard
  • dc.date.accessioned 2019-09-19T11:16:08Z
  • dc.date.available 2019-09-19T11:16:08Z
  • dc.date.issued 2019
  • dc.description.abstract Background: In order to prepare the genome for gametogenesis, primordial germ cells (PGCs) undergo extensive epigenetic reprogramming during migration toward the gonads in mammalian embryos. This includes changes on a genome-wide scale and additionally in females the remodeling of the inactive X-chromosome to enable X-chromosome reactivation (XCR). However, if global remodeling and X-chromosomal remodeling are related, how they occur in PGCs in vivo in relation to their migration progress and which factors are important are unknown. Results: Here we identify the germ cell determinant PR-domain containing protein 14 (PRDM14) as the first known factor that is instrumental for both global reprogramming and X-chromosomal reprogramming in migrating mouse PGCs. We find that global upregulation of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark is PRDM14 dosage dependent in PGCs of both sexes. When focusing on XCR, we observed that PRDM14 is required for removal of H3K27me3 from the inactive X-chromosome, which, in contrast to global upregulation, takes place progressively along the PGC migration path. Furthermore, we show that global and X-chromosomal reprogramming of H3K27me3 are functionally separable, despite their common regulation by PRDM14. Conclusions: In summary, here we provide new insight and spatiotemporal resolution to the progression and regulation of epigenome remodeling along mouse PGC migration in vivo and link epigenetic reprogramming to its developmental context.
  • dc.description.sponsorship This work has been funded by the Spanish Ministry of Science, Innovation and Universities (BFU2014-55275-P and BFU2017-88407-P), the AXA Research Fund and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346). We would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and to the “Centro de Excelencia Severo Ochoa.” We also acknowledge support of the CERCA Programme of the Generalitat de Catalunya.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Mallol A, Guirola M, Payer B. PRDM14 controls X-chromosomal and global epigenetic reprogramming of H3K27me3 in migrating mouse primordial germ cells. Epigenetics Chromatin. 2019;12(1):38. DOI: 10.1186/s13072-019-0284-7
  • dc.identifier.doi http://dx.doi.org/10.1186/s13072-019-0284-7
  • dc.identifier.issn 1756-8935
  • dc.identifier.uri http://hdl.handle.net/10230/42292
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Epigenetics Chromatin. 2019;12(1):38
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
  • dc.rights © 2019, Anna Mallol, Maria Guirola, Bernhard Payer.This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword PRDM14
  • dc.subject.keyword X-chromosome reactivation
  • dc.subject.keyword PGCs
  • dc.subject.keyword Epigenetic reprogramming
  • dc.subject.keyword H3K27me3
  • dc.subject.keyword Mouse
  • dc.title PRDM14 controls X-chromosomal and global epigenetic reprogramming of H3K27me3 in migrating mouse primordial germ cells
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion