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dc.contributor.authorLi, Yun
dc.contributor.authorWang, Haoyi
dc.contributor.authorMuffat, Julien
dc.contributor.authorCheng, Albert W.
dc.contributor.authorOrlando, David A.
dc.contributor.authorKwok, Show-ming
dc.contributor.authorFeldman, Danielle A.
dc.contributor.authorBateup, Helen S.
dc.contributor.authorGao, Qing
dc.contributor.authorHockemeyer, Dirk
dc.contributor.authorMitalipova, Maisam
dc.contributor.authorLewis, Caroline A.
dc.contributor.authorSur, Mriganka
dc.contributor.authorYoung, Richard A.
dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorLoven, Jakob
dc.contributor.authorVander Heiden, Matthew G.
dc.contributor.authorFeldman, Danielle A.
dc.contributor.authorLewis, Caroline A.
dc.contributor.authorYoung, Richard A.
dc.date.accessioned2016-05-18T17:10:26Z
dc.date.available2016-05-18T17:10:26Z
dc.date.issued2013-10
dc.identifier.issn19345909
dc.identifier.urihttp://hdl.handle.net/1721.1/102529
dc.description.abstractRett syndrome (RTT) is caused by mutations of MECP2, a methyl CpG binding protein thought to act as a global transcriptional repressor. Here we show, using an isogenic human embryonic stem cell model of RTT, that MECP2 mutant neurons display key molecular and cellular features of this disorder. Unbiased global gene expression analyses demonstrate that MECP2 functions as a global activator in neurons but not in neural precursors. Decreased transcription in neurons was coupled with a significant reduction in nascent protein synthesis and lack of MECP2 was manifested as a severe defect in the activity of the AKT/mTOR pathway. Lack of MECP2 also leads to impaired mitochondrial function in mutant neurons. Activation of AKT/mTOR signaling by exogenous growth factors or by depletion of PTEN boosted protein synthesis and ameliorated disease phenotypes in mutant neurons. Our findings indicate a vital function for MECP2 in maintaining active gene transcription in human neuronal cells.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01-HG002668)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (P30-CA14051)en_US
dc.description.sponsorshipDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.description.sponsorshipKathy and Curt Marble Cancer Research Funden_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant HD 045022)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R37-CA084198)en_US
dc.description.sponsorshipSimons Foundationen_US
dc.description.sponsorshipEuropean Leukodystrophy Associationen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.stem.2013.09.001en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleGlobal Transcriptional and Translational Repression in Human-Embryonic-Stem-Cell-Derived Rett Syndrome Neuronsen_US
dc.typeArticleen_US
dc.identifier.citationLi, Yun, Haoyi Wang, Julien Muffat, Albert W. Cheng, David A. Orlando, Jakob Loven, Show-ming Kwok, et al. “Global Transcriptional and Translational Repression in Human-Embryonic-Stem-Cell-Derived Rett Syndrome Neurons.” Cell Stem Cell 13, no. 4 (October 2013): 446–58.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorKwok, Show-mingen_US
dc.contributor.mitauthorFeldman, Danielle A.en_US
dc.contributor.mitauthorLewis, Caroline A.en_US
dc.contributor.mitauthorVander Heiden, Matthew G.en_US
dc.contributor.mitauthorSur, Mrigankaen_US
dc.contributor.mitauthorYoung, Richard A.en_US
dc.contributor.mitauthorJaenisch, Rudolfen_US
dc.relation.journalCell Stem Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLi, Yun; Wang, Haoyi; Muffat, Julien; Cheng, Albert W.; Orlando, David A.; Loven, Jakob; Kwok, Show-ming; Feldman, Danielle A.; Bateup, Helen S.; Gao, Qing; Hockemeyer, Dirk; Mitalipova, Maisam; Lewis, Caroline A.; Vander Heiden, Matthew G.; Sur, Mriganka; Young, Richard A.; Jaenisch, Rudolfen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
dc.identifier.orcidhttps://orcid.org/0000-0001-9168-0109
dc.identifier.orcidhttps://orcid.org/0000-0003-2442-5671
dc.identifier.orcidhttps://orcid.org/0000-0001-8855-8647
dc.identifier.orcidhttps://orcid.org/0000-0002-6883-3805
mit.licensePUBLISHER_CCen_US


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