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- Publisher Website: 10.1038/ncb1786
- Scopus: eid_2-s2.0-55549119925
- PMID: 18836439
- WOS: WOS:000260586700010
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Article: Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5
Title | Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5 | ||||||||||||||||
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Authors | |||||||||||||||||
Issue Date | 2008 | ||||||||||||||||
Publisher | Nature 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? | ||||||||||||||||
Abstract | Mouse 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 Identifier | http://hdl.handle.net/10722/148588 | ||||||||||||||||
ISSN | 2023 Impact Factor: 17.3 2023 SCImago Journal Rankings: 8.913 | ||||||||||||||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Ng, RK | en_US |
dc.contributor.author | Dean, W | en_US |
dc.contributor.author | Dawson, C | en_US |
dc.contributor.author | Lucifero, D | en_US |
dc.contributor.author | Madeja, Z | en_US |
dc.contributor.author | Reik, W | en_US |
dc.contributor.author | Hemberger, M | en_US |
dc.date.accessioned | 2012-05-29T06:13:56Z | - |
dc.date.available | 2012-05-29T06:13:56Z | - |
dc.date.issued | 2008 | en_US |
dc.identifier.citation | Nature Cell Biology, 2008, v. 10 n. 11, p. 1280-1290 | en_US |
dc.identifier.issn | 1465-7392 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/148588 | - |
dc.description.abstract | Mouse 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.language | eng | en_US |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/naturecellbiology | en_US |
dc.relation.ispartof | Nature Cell Biology | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Cell Differentiation - Genetics - Physiology | en_US |
dc.subject.mesh | Cell Lineage - Genetics | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Dna Methylation - Genetics | en_US |
dc.subject.mesh | Dna-Binding Proteins - Genetics - Metabolism | en_US |
dc.subject.mesh | Embryo, Mammalian - Metabolism | en_US |
dc.subject.mesh | Embryonic Stem Cells - Metabolism - Physiology | en_US |
dc.subject.mesh | Epigenesis, Genetic | en_US |
dc.subject.mesh | Gene Expression Regulation, Developmental | en_US |
dc.subject.mesh | In Situ Hybridization | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Models, Biological | en_US |
dc.subject.mesh | Transcription Factors - Genetics - Metabolism | en_US |
dc.title | Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5 | en_US |
dc.type | Article | en_US |
dc.identifier.email | Ng, RK:rayng@pathology.hku.hk | en_US |
dc.identifier.authority | Ng, RK=rp00273 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1038/ncb1786 | en_US |
dc.identifier.pmid | 18836439 | - |
dc.identifier.scopus | eid_2-s2.0-55549119925 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-55549119925&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 10 | en_US |
dc.identifier.issue | 11 | en_US |
dc.identifier.spage | 1280 | en_US |
dc.identifier.epage | 1290 | en_US |
dc.identifier.eissn | 1476-4679 | - |
dc.identifier.isi | WOS:000260586700010 | - |
dc.publisher.place | United Kingdom | en_US |
dc.identifier.f1000 | 1123260 | - |
dc.identifier.citeulike | 3447288 | - |
dc.identifier.issnl | 1465-7392 | - |