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Targeting H3K4 trimethylation in Huntington disease

dc.contributor.authorNg, Christopher W.
dc.contributor.authorYildirim, Ferah
dc.contributor.authorLabadorf, Adam
dc.contributor.authorFraenkel, Ernest
dc.contributor.authorVashishtha, Malini
dc.contributor.authorKratter, Ian H.
dc.contributor.authorBodai, Laszlo
dc.contributor.authorSong, Wan
dc.contributor.authorLau, Alice L.
dc.contributor.authorVogel-Ciernia, Annie
dc.contributor.authorTroncosco, Juan
dc.contributor.authorRoss, Christopher A.
dc.contributor.authorBates, Gillian P.
dc.contributor.authorKrainc, Dimitri
dc.contributor.authorSadri-Vakili, Ghazaleh
dc.contributor.authorFinkbeiner, Steven
dc.contributor.authorMarsh, J. Lawrence
dc.contributor.authorThompson, Leslie M.
dc.contributor.authorWasylenko, Theresa Anne
dc.contributor.authorHousman, David E
dc.date.accessioned2014-03-24T18:35:41Z
dc.date.available2014-03-24T18:35:41Z
dc.date.issued2013-08
dc.date.submitted2013-05
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/85912
dc.description.abstractTranscriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant U54-CA112967)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01-GM089903)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant PN2EY016525)en_US
dc.description.sponsorshipHereditary Disease Foundation (U.S.) (Leslie Gehry Brenner Award for Innovation in Science)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1311323110en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceNational Academy of Science (U.S.)en_US
dc.titleTargeting H3K4 trimethylation in Huntington diseaseen_US
dc.typeArticleen_US
dc.identifier.citationVashishtha, M., C. W. Ng, F. Yildirim, T. A. Gipson, I. H. Kratter, L. Bodai, W. Song, et al. “Targeting H3K4 Trimethylation in Huntington Disease.” Proceedings of the National Academy of Sciences 110, no. 32 (August 6, 2013): E3027–E3036.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorNg, Christopher W.en_US
dc.contributor.mitauthorYildirim, Ferahen_US
dc.contributor.mitauthorGipson, Theresa Anneen_US
dc.contributor.mitauthorLabadorf, Adamen_US
dc.contributor.mitauthorHousman, David E.en_US
dc.contributor.mitauthorFraenkel, Ernesten_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsVashishtha, M.; Ng, C. W.; Yildirim, F.; Gipson, T. A.; Kratter, I. H.; Bodai, L.; Song, W.; Lau, A.; Labadorf, A.; Vogel-Ciernia, A.; Troncosco, J.; Ross, C. A.; Bates, G. P.; Krainc, D.; Sadri-Vakili, G.; Finkbeiner, S.; Marsh, J. L.; Housman, D. E.; Fraenkel, E.; Thompson, L. M.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-0524-5301
dc.identifier.orcidhttps://orcid.org/0000-0003-1381-4313
dc.identifier.orcidhttps://orcid.org/0000-0001-9249-8181
dc.identifier.orcidhttps://orcid.org/0000-0001-5016-0756
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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