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dc.contributor.authorLoven, Jakob
dc.contributor.authorHoke, Heather Ashley
dc.contributor.authorLin, Charles Y.
dc.contributor.authorLau, Ashley
dc.contributor.authorOrlando, David A.
dc.contributor.authorVakoc, Christopher R.
dc.contributor.authorBradner, James E.
dc.contributor.authorLee, Tong Ihn
dc.contributor.authorYoung, Richard A.
dc.date.accessioned2014-05-01T16:20:12Z
dc.date.available2014-05-01T16:20:12Z
dc.date.issued2013-04
dc.date.submitted2013-02
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/86330
dc.description.abstractChromatin regulators have become attractive targets for cancer therapy, but it is unclear why inhibition of these ubiquitous regulators should have gene-specific effects in tumor cells. Here, we investigate how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition of the MYC oncogene in multiple myeloma (MM). BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. They also co-occupied a small set of exceptionally large super-enhancers associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impacted genes with super-enhancers, including MYC. Super-enhancers were found at key oncogenic drivers in many other tumor cells. These observations have implications for the discovery of cancer therapeutics directed at components of super-enhancers in diverse tumor types.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant HG002668)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant CA146445)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2013.03.036en_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.sourceElsevier Open Accessen_US
dc.titleSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancersen_US
dc.typeArticleen_US
dc.identifier.citationLoven, Jakob, Heather A. Hoke, Charles Y. Lin, Ashley Lau, David A. Orlando, Christopher R. Vakoc, James E. Bradner, Tong Ihn Lee, and Richard A. Young. “Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers.” Cell 153, no. 2 (April 2013): 320–334. © 2013 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorHoke, Heather Ashleyen_US
dc.contributor.mitauthorLin, Charles Y.en_US
dc.contributor.mitauthorLau, Ashleyen_US
dc.contributor.mitauthorYoung, Richard A.en_US
dc.relation.journalCellen_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.orderedauthorsLovén, Jakob; Hoke, Heather A.; Lin, Charles Y.; Lau, Ashley; Orlando, David A.; Vakoc, Christopher R.; Bradner, James E.; Lee, Tong Ihn; Young, Richard A.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4549-5425
dc.identifier.orcidhttps://orcid.org/0000-0001-8855-8647
mit.licensePUBLISHER_POLICYen_US


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