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dc.contributor.authorAlotaibi, H.en_US
dc.contributor.authorBasilicata, M. F.en_US
dc.contributor.authorShehwana, H.en_US
dc.contributor.authorKosowan, T.en_US
dc.contributor.authorSchreck, I.en_US
dc.contributor.authorBraeutigam, C.en_US
dc.contributor.authorKonu, O.en_US
dc.contributor.authorBrabletz, T.en_US
dc.contributor.authorStemmler, M. P.en_US
dc.date.accessioned2016-02-08T10:09:51Z
dc.date.available2016-02-08T10:09:51Z
dc.date.issued2015en_US
dc.identifier.issn1874-9399
dc.identifier.urihttp://hdl.handle.net/11693/23170
dc.description.abstractEpithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) highlight crucial steps during embryogenesis and tumorigenesis. Induction of dramatic changes in gene expression and cell features is reflected by modulation of Cdh1 (E-cadherin) expression. We show that Cdh1 activity during MET is governed by two enhancers at +. 7.8. kb and at +. 11.5. kb within intron 2 that are activated by binding of Grhl3 and Hnf4α, respectively. Recruitment of Grhl3 and Hnf4α to the enhancers is crucial for activating Cdh1 and accomplishing MET in non-tumorigenic mouse mammary gland cells (NMuMG). Moreover, the two enhancers cooperate via Grhl3 and Hnf4α binding, induction of DNA-looping and clustering at the promoter to orchestrate E-cadherin re-expression. Our results provide novel insights into the cellular mechanisms whereby cells respond to MET signals and re-establish an epithelial phenotype by enhancer cooperativity. A general importance of our findings including MET-mediated colonization of metastasizing tumor cells is suggested.en_US
dc.language.isoEnglishen_US
dc.source.titleBiochimica et Biophysica Acta - Gene Regulatory Mechanismsen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.bbagrm.2015.01.005en_US
dc.subjectCadherinsen_US
dc.subjectCanceren_US
dc.subjectDevelopmenten_US
dc.subjectGrhl3en_US
dc.subjectHnf4αen_US
dc.subjectTransforming growth factor betaen_US
dc.subjectCadherinsen_US
dc.subjectDna-binding proteinsen_US
dc.subjectGrhl3 proteinen_US
dc.subjectHepatocyte Nuclear Factor 4en_US
dc.subjectHnf4a proteinen_US
dc.subjectTranscription Factorsen_US
dc.subjectAnimalsen_US
dc.subjectBiosynthesisen_US
dc.subjectCell transformationen_US
dc.subjectEnhancer elementsen_US
dc.subjectEpithelial-mesenchymal transitionen_US
dc.subjectGene Expression Regulationen_US
dc.subjectGeneticsen_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectPromoter Regionsen_US
dc.subjectTranscriptionen_US
dc.subjectAnimalsen_US
dc.subjectCadherinsen_US
dc.subjectCell Transformationen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectEnhancer Elementsen_US
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectGene Expression Regulationen_US
dc.subjectHepatocyte Nuclear Factor 4en_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectPromoter Regionsen_US
dc.subjectTranscription Factorsen_US
dc.subjectTranscriptionen_US
dc.titleEnhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transitionen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage731en_US
dc.citation.epage742en_US
dc.citation.volumeNumber1849en_US
dc.citation.issueNumber6en_US
dc.identifier.doi10.1016/j.bbagrm.2015.01.005en_US
dc.publisherElsevieren_US


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