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Article: Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm

TitleOct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm
Authors
Keywordsenhancer code
endoderm
Sox/Oct interaction
pluripotency
lineage specification
Issue Date2013
Citation
EMBO Journal, 2013, v. 32, n. 7, p. 938-953 How to Cite?
AbstractHow regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique 'compressed' Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at 'canonical' binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point-mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome. © 2013 European Molecular Biology Organization.
Persistent Identifierhttp://hdl.handle.net/10722/253105
ISSN
2020 Impact Factor: 11.598
2020 SCImago Journal Rankings: 7.484
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAksoy, Irene-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorChen, Jiaxuan-
dc.contributor.authorDyla, Mateusz-
dc.contributor.authorDivakar, Ushashree-
dc.contributor.authorBogu, Gireesh K.-
dc.contributor.authorTeo, Roy-
dc.contributor.authorLeng Ng, Calista Keow-
dc.contributor.authorHerath, Wishva-
dc.contributor.authorLili, Sun-
dc.contributor.authorHutchins, Andrew P.-
dc.contributor.authorRobson, Paul-
dc.contributor.authorKolatkar, Prasanna R.-
dc.contributor.authorStanton, Lawrence W.-
dc.date.accessioned2018-05-11T05:38:36Z-
dc.date.available2018-05-11T05:38:36Z-
dc.date.issued2013-
dc.identifier.citationEMBO Journal, 2013, v. 32, n. 7, p. 938-953-
dc.identifier.issn0261-4189-
dc.identifier.urihttp://hdl.handle.net/10722/253105-
dc.description.abstractHow regulatory information is encoded in the genome is poorly understood and poses a challenge when studying biological processes. We demonstrate here that genomic redistribution of Oct4 by alternative partnering with Sox2 and Sox17 is a fundamental regulatory event of endodermal specification. We show that Sox17 partners with Oct4 and binds to a unique 'compressed' Sox/Oct motif that earmarks endodermal genes. This is in contrast to the pluripotent state where Oct4 selectively partners with Sox2 at 'canonical' binding sites. The distinct selection of binding sites by alternative Sox/Oct partnering is underscored by our demonstration that rationally point-mutated Sox17 partners with Oct4 on pluripotency genes earmarked by the canonical Sox/Oct motif. In an endodermal differentiation assay, we demonstrate that the compressed motif is required for proper expression of endodermal genes. Evidently, Oct4 drives alternative developmental programs by switching Sox partners that affects enhancer selection, leading to either an endodermal or pluripotent cell fate. This work provides insights in understanding cell fate transcriptional regulation by highlighting the direct link between the DNA sequence of an enhancer and a developmental outcome. © 2013 European Molecular Biology Organization.-
dc.languageeng-
dc.relation.ispartofEMBO Journal-
dc.subjectenhancer code-
dc.subjectendoderm-
dc.subjectSox/Oct interaction-
dc.subjectpluripotency-
dc.subjectlineage specification-
dc.titleOct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/emboj.2013.31-
dc.identifier.pmid23474895-
dc.identifier.scopuseid_2-s2.0-84875940444-
dc.identifier.volume32-
dc.identifier.issue7-
dc.identifier.spage938-
dc.identifier.epage953-
dc.identifier.eissn1460-2075-
dc.identifier.isiWOS:000317040600006-
dc.identifier.issnl0261-4189-

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