Show simple item record

dc.contributor.authorNascimento, Elisabete M
dc.contributor.authorCox, Claire L
dc.contributor.authorMacArthur, Stewart
dc.contributor.authorHussain, Shobbir
dc.contributor.authorTrotter, Matthew
dc.contributor.authorBlanco, Sandra
dc.contributor.authorSuraj, Menon
dc.contributor.authorNichols, Jennifer
dc.contributor.authorKübler, Bernd
dc.contributor.authorBenitah, Salvador Aznar
dc.contributor.authorHendrich, Brian
dc.contributor.authorOdom, Duncan T
dc.contributor.authorFrye, Michaela
dc.date.accessioned2020-02-01T00:30:57Z
dc.date.available2020-02-01T00:30:57Z
dc.date.issued2011-11-20
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301550
dc.description.abstractHow the proto-oncogene c-Myc balances the processes of stem-cell self-renewal, proliferation and differentiation in adult tissues is largely unknown. We explored c-Myc's transcriptional roles at the epidermal differentiation complex, a locus essential for skin maturation. Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes. We found that Sin3a causes deacetylation of c-Myc protein to directly repress c-Myc activity. In the absence of Sin3a, genomic recruitment of c-Myc to the epidermal differentiation complex is enhanced, and re-activation of c-Myc-target genes drives aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3a reverts the skin phenotype to normal. Our results identify how the balance of two transcriptional key regulators can maintain tissue homeostasis through a negative feedback loop.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.subjectEpidermis
dc.subjectKeratinocytes
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred CBA
dc.subjectMice, Transgenic
dc.subjectMice
dc.subjectProto-Oncogene Proteins c-myc
dc.subjectRepressor Proteins
dc.subjectTranscription, Genetic
dc.subjectHomeostasis
dc.subjectFemale
dc.subjectMale
dc.subjectFeedback, Physiological
dc.subjectSin3 Histone Deacetylase and Corepressor Complex
dc.subjectPrimary Cell Culture
dc.subjectEpidermal Cells
dc.titleThe opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis.
dc.typeArticle
prism.endingPage1405
prism.issueIdentifier12
prism.publicationDate2011
prism.publicationNameNat Cell Biol
prism.startingPage1395
prism.volume13
dc.identifier.doi10.17863/CAM.48619
dcterms.dateAccepted2011-10-21
rioxxterms.versionofrecord10.1038/ncb2385
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2011-11-20
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.contributor.orcidHendrich, Brian [0000-0002-0231-3073]
dc.contributor.orcidOdom, Duncan [0000-0001-6201-5599]
dc.contributor.orcidFrye, Michaela [0000-0002-5636-6840]
dc.identifier.eissn1476-4679
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G0800784)
pubs.funder-project-idMedical Research Council (G0801904)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idWellcome Trust (098021/Z/11/Z)
pubs.funder-project-idEuropean Research Council (202218)
cam.issuedOnline2011-11-20
rioxxterms.freetoread.startdate2012-05-20


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record