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Article: Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5

TitleEpigenetic restriction of embryonic cell lineage fate by methylation of Elf5
Authors
Issue Date2008
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology
Citation
Nature Cell Biology, 2008, v. 10 n. 11, p. 1280-1290 How to Cite?
AbstractMouse ES cells can differentiate into all three germ layers of the embryo but are generally excluded from the trophoblast lineage. Here we show that ES cells deficient in DNA methylation can differentiate efficiently into trophoblast derivatives. In a genome-wide screen we identified the transcription factor Elf5 as methylated and repressed in ES cells, and hypomethylated and expressed in TS and methylation-deficient ES cells. Elf5 creates a positive-feedback loop with the TS cell determinants Cdx2 and Eomes that is restricted to the trophoblast lineage by epigenetic regulation of Elf5. Importantly, the late-acting function of Elf5 allows initial plasticity and regulation in the early blastocyst. Thus, Elf5 functions as a gatekeeper, downstream of initial lineage determination, to reinforce commitment to the trophoblast lineage or to abort this pathway in epiblast cells. This epigenetic restriction of cell lineage fate provides a molecular mechanism for Waddington's concept of canalization of developmental pathways.
Persistent Identifierhttp://hdl.handle.net/10722/148588
ISSN
2015 Impact Factor: 18.699
2015 SCImago Journal Rankings: 14.131
ISI Accession Number ID
Funding AgencyGrant Number
MRC Career Development Award
Croucher Foundation
BBSRC
MRC
EU NoE The Epigenome
CellCentric
DIUS
Funding Information:

We would like to thank Fatima Santos and Annabelle Lewis for expert help with confocal microscopy and qPCR design, respectively. We also thank En Li for Dnmt1- mice and ES cells, and Haruhiko Koseki, Nick Gilbert and David Skalnik for ES cell lines. This work was supported by an MRC Career Development Award to M. H., by the Croucher Foundation Fellowship to R. K. N., and by BBSRC, MRC, EU NoE The Epigenome, CellCentric, and DIUS.

References

 

DC FieldValueLanguage
dc.contributor.authorNg, RKen_US
dc.contributor.authorDean, Wen_US
dc.contributor.authorDawson, Cen_US
dc.contributor.authorLucifero, Den_US
dc.contributor.authorMadeja, Zen_US
dc.contributor.authorReik, Wen_US
dc.contributor.authorHemberger, Men_US
dc.date.accessioned2012-05-29T06:13:56Z-
dc.date.available2012-05-29T06:13:56Z-
dc.date.issued2008en_US
dc.identifier.citationNature Cell Biology, 2008, v. 10 n. 11, p. 1280-1290en_US
dc.identifier.issn1465-7392en_US
dc.identifier.urihttp://hdl.handle.net/10722/148588-
dc.description.abstractMouse ES cells can differentiate into all three germ layers of the embryo but are generally excluded from the trophoblast lineage. Here we show that ES cells deficient in DNA methylation can differentiate efficiently into trophoblast derivatives. In a genome-wide screen we identified the transcription factor Elf5 as methylated and repressed in ES cells, and hypomethylated and expressed in TS and methylation-deficient ES cells. Elf5 creates a positive-feedback loop with the TS cell determinants Cdx2 and Eomes that is restricted to the trophoblast lineage by epigenetic regulation of Elf5. Importantly, the late-acting function of Elf5 allows initial plasticity and regulation in the early blastocyst. Thus, Elf5 functions as a gatekeeper, downstream of initial lineage determination, to reinforce commitment to the trophoblast lineage or to abort this pathway in epiblast cells. This epigenetic restriction of cell lineage fate provides a molecular mechanism for Waddington's concept of canalization of developmental pathways.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiologyen_US
dc.relation.ispartofNature Cell Biologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Differentiation - Genetics - Physiologyen_US
dc.subject.meshCell Lineage - Geneticsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDna Methylation - Geneticsen_US
dc.subject.meshDna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshEmbryo, Mammalian - Metabolismen_US
dc.subject.meshEmbryonic Stem Cells - Metabolism - Physiologyen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshGene Expression Regulation, Developmentalen_US
dc.subject.meshIn Situ Hybridizationen_US
dc.subject.meshMiceen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshTranscription Factors - Genetics - Metabolismen_US
dc.titleEpigenetic restriction of embryonic cell lineage fate by methylation of Elf5en_US
dc.typeArticleen_US
dc.identifier.emailNg, RK:rayng@pathology.hku.hken_US
dc.identifier.authorityNg, RK=rp00273en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ncb1786en_US
dc.identifier.pmid18836439-
dc.identifier.scopuseid_2-s2.0-55549119925en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-55549119925&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue11en_US
dc.identifier.spage1280en_US
dc.identifier.epage1290en_US
dc.identifier.eissn1476-4679-
dc.identifier.isiWOS:000260586700010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.f10001123260-
dc.identifier.citeulike3447288-

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