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dc.contributor.authorYang, Xiaofang
dc.contributor.authorPursell, Bryan
dc.contributor.authorLu, Shaolei
dc.contributor.authorChang, Tsun-Kai
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:09:39.000
dc.date.accessioned2022-08-23T16:38:54Z
dc.date.available2022-08-23T16:38:54Z
dc.date.issued2009-06-25
dc.date.submitted2010-04-01
dc.identifier.citation<p>J Cell Sci. 2009 Jul 15;122(Pt 14):2473-80. Epub 2009 Jun 23. <a href="http://dx.doi.org/10.1242/jcs.049148">Link to article on publisher's site</a></p>
dc.identifier.issn0021-9533 (Linking)
dc.identifier.doi10.1242/jcs.049148
dc.identifier.pmid19549682
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39353
dc.description.abstractThe beta 4 integrin is expressed in epithelial cells, a few other cell types and in some carcinomas. Despite this restricted expression pattern and the functional importance of beta 4 integrin in epithelial and carcinoma biology, little is known about how its expression is regulated. Here, we assessed the epigenetic regulation of beta 4 integrin based on the presence of a large CpG island in the beta 4-integrin gene promoter. We separated basal (beta 4+) and luminal (beta 4-) epithelial cells from the mammary glands of K14-eGFP mice and demonstrated that the beta 4-integrin promoter is unmethylated in basal cells and methylated in luminal cells. We also observed that expression of beta 4 integrin and E-cadherin is lost during the epithelial-to-mesenchymal transition (EMT) of mammary gland cells induced by transforming growth factor beta (TGFbeta), which is coincident with de novo DNA methylation, a decrease in active histone modifications (H3K9Ac and H3K4me3) and an increase in the repressive histone modification H3K27me3. Furthermore, TGFbeta withdrawal promotes a mesenchymal-to-epithelial transition (MET) and triggers the re-expression of beta 4 integrin and E-cadherin. Intriguingly, demethylation at either promoter is not obligatory for transcriptional reactivation after TGFbeta withdrawal. However, both H3K9Ac and H3K4me3 modifications are restored during the MET, and H3K27me3 is reduced, strongly suggesting that reversible histone modifications rather than DNA demethylation are the predominant factors in reactivating expression of these genes. Our data indicate that complex epigenetic modifications contribute to the regulation of the beta 4 integrin and E-cadherin.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19549682&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704882/
dc.subjectAnimals
dc.subjectCadherins
dc.subjectCell Line
dc.subjectCell Transdifferentiation
dc.subjectCpG Islands
dc.subject*DNA Methylation
dc.subjectEpithelial Cells
dc.subjectFemale
dc.subjectHistones
dc.subjectIntegrin beta4
dc.subjectMammary Glands, Animal
dc.subjectMesoderm
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectPromoter Regions, Genetic
dc.subjectTranscriptional Activation
dc.subjectTransforming Growth Factor beta
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleRegulation of beta 4-integrin expression by epigenetic modifications in the mammary gland and during the epithelial-to-mesenchymal transition
dc.typeArticle
dc.source.journaltitleJournal of cell science
dc.source.volume122
dc.source.issuePt 14
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2152
dc.identifier.contextkey1257929
html.description.abstract<p>The beta 4 integrin is expressed in epithelial cells, a few other cell types and in some carcinomas. Despite this restricted expression pattern and the functional importance of beta 4 integrin in epithelial and carcinoma biology, little is known about how its expression is regulated. Here, we assessed the epigenetic regulation of beta 4 integrin based on the presence of a large CpG island in the beta 4-integrin gene promoter. We separated basal (beta 4+) and luminal (beta 4-) epithelial cells from the mammary glands of K14-eGFP mice and demonstrated that the beta 4-integrin promoter is unmethylated in basal cells and methylated in luminal cells. We also observed that expression of beta 4 integrin and E-cadherin is lost during the epithelial-to-mesenchymal transition (EMT) of mammary gland cells induced by transforming growth factor beta (TGFbeta), which is coincident with de novo DNA methylation, a decrease in active histone modifications (H3K9Ac and H3K4me3) and an increase in the repressive histone modification H3K27me3. Furthermore, TGFbeta withdrawal promotes a mesenchymal-to-epithelial transition (MET) and triggers the re-expression of beta 4 integrin and E-cadherin. Intriguingly, demethylation at either promoter is not obligatory for transcriptional reactivation after TGFbeta withdrawal. However, both H3K9Ac and H3K4me3 modifications are restored during the MET, and H3K27me3 is reduced, strongly suggesting that reversible histone modifications rather than DNA demethylation are the predominant factors in reactivating expression of these genes. Our data indicate that complex epigenetic modifications contribute to the regulation of the beta 4 integrin and E-cadherin.</p>
dc.identifier.submissionpathoapubs/2152
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages2473-80


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