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dc.contributor.authordos, Santos Camila Oen
dc.contributor.authorDolzhenko, Egoren
dc.contributor.authorHodges, Emilyen
dc.contributor.authorSmith, Andrew Den
dc.contributor.authorHannon, Gregoryen
dc.date.accessioned2015-10-28T10:59:58Z
dc.date.available2015-10-28T10:59:58Z
dc.date.issued2015-05-07en
dc.identifier.citationCell Reports 2015, 11(7), 1102-1109. doi: 10.1016/j.celrep.2015.04.015en
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252422
dc.description.abstractPregnancy is the major modulator of mammary gland activity. It induces a tremendous expansion of the mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the mammary gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here, we verify that the mouse mammary gland responds more robustly to a second pregnancy, indicating that the gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated mammary cell types reveals substantial and long-lasting alterations. Since these alterations are maintained in the absence of the signal that induced them, we term them epigenetic. The majority of alterations in DNA methylation affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote mammary gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.
dc.description.sponsorshipWe thank Antoine Molaro for helpful discussions. This work was performed with assistance from the CSHL Flow Cytometry Shared Resource and from the CSHL Histology Shared Resource, which are supported by Cancer Center Support Grant 5P30CA045508. This work was supported by the NIH Grand Opportunity award #1 RC2 CA148507 (G.J.H.), P01 award # 2P01CA013106 (G.J.H.), and NIH grant R01 H6005238 (A.D.S.). G.J.H. is an investigator of the Howard Hughes Medical Institute.
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivs 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.0/uk/*
dc.titleAn Epigenetic Memory of Pregnancy in the Mouse Mammary Glanden
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2015.04.015en
prism.endingPage1109
prism.publicationDate2015en
prism.publicationNameCell Reportsen
prism.startingPage1102
prism.volume11en
dc.rioxxterms.funderNIH
dc.rioxxterms.projectid5P30CA045508
dc.rioxxterms.projectidRC2 CA148507
dc.rioxxterms.projectidP01CA013106
dc.rioxxterms.projectidR01 H6005238
dcterms.dateAccepted2015-04-06en
rioxxterms.versionofrecord10.1016/j.celrep.2015.04.015en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-05-07en
dc.contributor.orcidHannon, Gregory [0000-0003-4021-3898]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Reviewen


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Attribution-NonCommercial-NoDerivs 2.0 UK: England & Wales
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