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dc.contributor.authorSarma, Kavitha
dc.contributor.authorLee, Jeannie T.
dc.contributor.authorDimitrova, Nadya
dc.contributor.authorZamudio, Jesse Ray
dc.contributor.authorJong, Robyn
dc.contributor.authorSoukup, Dylan S.
dc.contributor.authorResnick, Rebecca
dc.contributor.authorWhipple, Amanda Joy
dc.contributor.authorRaj, Arjun
dc.contributor.authorSharp, Phillip A.
dc.contributor.authorJacks, Tyler E.
dc.date.accessioned2017-06-30T19:55:11Z
dc.date.available2017-06-30T19:55:11Z
dc.date.issued2014-05
dc.date.submitted2014-11
dc.identifier.issn1097-2765
dc.identifier.issn1097-4164
dc.identifier.urihttp://hdl.handle.net/1721.1/110403
dc.description.abstractThe p53-regulated long noncoding RNA lincRNA-p21 has been proposed to act in trans via several mechanisms ranging from repressing genes in the p53 transcriptional network to regulating mRNA translation and protein stability. To further examine lincRNA-p21 function, we generated a conditional knockout mouse model. We find that lincRNA-p21 predominantly functions in cis to activate expression of its neighboring gene, p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a coactivator for p53-dependent p21 transcription. Additional phenotypes of lincRNA-p21 deficiency could be attributed to diminished p21 levels, including deregulated expression and altered chromatin state of some Polycomb target genes, a defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency. These findings indicate that lincRNA-p21 affects global gene expression and influences the p53 tumor suppressor pathway by acting in cis as a locus-restricted coactivator for p53-mediated p21 expression.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.)en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.description.sponsorshipLudwig Center for Molecular Oncologyen_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundationen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.molcel.2014.04.025en_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.titleLincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpointen_US
dc.typeArticleen_US
dc.identifier.citationDimitrova, Nadya, Jesse R. Zamudio, Robyn M. Jong, Dylan Soukup, Rebecca Resnick, Kavitha Sarma, Amanda J. Ward, et al. “LincRNA-P21 Activates P21 In Cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint.” Molecular Cell 54, no. 5 (June 2014): 777–790.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorDimitrova, Nadya
dc.contributor.mitauthorZamudio, Jesse Ray
dc.contributor.mitauthorJong, Robyn
dc.contributor.mitauthorSoukup, Dylan S.
dc.contributor.mitauthorResnick, Rebecca
dc.contributor.mitauthorWhipple, Amanda Joy
dc.contributor.mitauthorRaj, Arjun
dc.contributor.mitauthorSharp, Phillip A.
dc.contributor.mitauthorJacks, Tyler E.
dc.relation.journalMolecular 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.orderedauthorsDimitrova, Nadya; Zamudio, Jesse R.; Jong, Robyn M.; Soukup, Dylan; Resnick, Rebecca; Sarma, Kavitha; Ward, Amanda J.; Raj, Arjun; Lee, Jeannie T.; Sharp, Phillip A.; Jacks, Tyleren_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-0019-5296
dc.identifier.orcidhttps://orcid.org/0000-0003-1465-1691
dc.identifier.orcidhttps://orcid.org/0000-0001-5785-8911
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen_US


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