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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:p>\n                    Long thought to be dispensable after establishing X chromosome inactivation (XCI), Xist RNA is now known to also maintain the inactive X (Xi). To what extent somatic X reactivation causes physiological abnormalities is an active area of inquiry. Here, we use multiple mouse models to investigate in vivo consequences. First, when\n                    <jats:italic>Xist<\/jats:italic>\n                    is deleted systemically in post-XCI embryonic cells using the Meox2-Cre driver, female pups exhibit no morbidity or mortality despite partial X reactivation. Second, when\n                    <jats:italic>Xist<\/jats:italic>\n                    is conditionally deleted in epithelial cells using Keratin14-Cre or in B cells using CD19-Cre, female mice have a normal life span without obvious illness. Third, when\n                    <jats:italic>Xist<\/jats:italic>\n                    is deleted in gut using Villin-Cre, female mice remain healthy despite significant X\u2013autosome dosage imbalance. Finally, when the gut is acutely stressed by azoxymethane\/dextran sulfate (AOM\/DSS) exposure, both\n                    <jats:italic>Xist<\/jats:italic>\n                    -deleted and wild-type mice develop gastrointestinal tumors. Intriguingly, however, under prolonged stress, mutant mice develop larger tumors and have a higher tumor burden. The effect is female specific. Altogether, these observations reveal a surprising systemic tolerance to Xist loss but importantly reveal that\n                    <jats:italic>Xist<\/jats:italic>\n                    and XCI are protective to females during chronic stress.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1917203117","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T20:24:42Z","timestamp":1581366282000},"page":"4262-4272","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":55,"title":["Widespread organ tolerance to Xist loss and X reactivation except under chronic stress in the gut"],"prefix":"10.1073","volume":"117","author":[{"given":"Lin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eda","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-4500","authenticated-orcid":false,"given":"James E.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Press","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannie T.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/dev.025908","article-title":"A new model for random X chromosome inactivation","volume":"136","author":"Starmer J.","year":"2009","unstructured":"J. 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