{"data":{"id":"10.6084/m9.figshare.c.2063219.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2063219.v1","prefix":"10.6084","suffix":"m9.figshare.c.2063219.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Sengupta, Deepanwita","givenName":"Deepanwita","familyName":"Sengupta","affiliation":[],"nameIdentifiers":[]},{"name":"Kannan, Aarthi","givenName":"Aarthi","familyName":"Kannan","affiliation":[],"nameIdentifiers":[]},{"name":"Kern, Malan","givenName":"Malan","familyName":"Kern","affiliation":[],"nameIdentifiers":[]},{"name":"A Moreno, Mauricio","givenName":"Mauricio","familyName":"A Moreno","affiliation":[],"nameIdentifiers":[]},{"name":"Vural, Emre","givenName":"Emre","familyName":"Vural","affiliation":[],"nameIdentifiers":[]},{"name":"Stack Jr, Brendan","givenName":"Brendan","familyName":"Stack Jr","affiliation":[],"nameIdentifiers":[]},{"name":"Y Suen, James","givenName":"James","familyName":"Y Suen","affiliation":[],"nameIdentifiers":[]},{"name":"J Tackett, Alan","givenName":"Alan","familyName":"J Tackett","affiliation":[],"nameIdentifiers":[]},{"name":"Gao, Ling","givenName":"Ling","familyName":"Gao","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Hematology"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Neuroscience"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Biochemistry"},{"subject":"Biophysics"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.c.2063219","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super-enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor JQ1 disrupts BRD4 association with super-enhancers, downregulates proto-oncogenes, such as \u003ci\u003ec-Myc\u003c/i\u003e, and displays antitumor activity in preclinical animal models of human cancers. Here we show that an enhancer proximal to the \u003ci\u003ec-Myc\u003c/i\u003e promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and coincides with a putative \u003ci\u003ec-Myc\u003c/i\u003e super-enhancer in MCC cells. This observation is mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the putative \u003ci\u003ec-Myc\u003c/i\u003e super-enhancer region by JQ1 correlates with decreased c-Myc expression. Thus, our study provides initial evidence that super-enhancers regulate c-Myc expression in MCC.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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