{"data":{"id":"10.6084/m9.figshare.1404170.v2","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1404170.v2","prefix":"10.6084","suffix":"m9.figshare.1404170.v2","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":"2015-07-13","dateType":"Created"},{"date":"2023-10-18","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.1404170","relatedIdentifierType":"DOI"},{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15592294.2015.1034416","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1913478 Bytes"],"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":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjQvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLjE0MDQxNzAuVjI8L2lkZW50aWZpZXI+CiAgPGNyZWF0b3JzPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5EZWVwYW53aXRhIFNlbmd1cHRhPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5EZWVwYW53aXRhPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPlNlbmd1cHRhPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5BYXJ0aGkgS2FubmFuPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5BYXJ0aGk8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+S2FubmFuPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5NYWxhbiBLZXJuPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5NYWxhbjwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5LZXJuPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5NYXVyaWNpbyBBIE1vcmVubzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+TWF1cmljaW88L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+QSBNb3Jlbm88L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkVtcmUgVnVyYWw8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkVtcmU8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+VnVyYWw8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkJyZW5kYW4gU3RhY2sgSnI8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkJyZW5kYW48L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+U3RhY2sgSnI8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkphbWVzIFkgU3VlbjwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+SmFtZXM8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+WSBTdWVuPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5BbGFuIEogVGFja2V0dDwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+QWxhbjwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5KIFRhY2tldHQ8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkxpbmcgR2FvPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5MaW5nPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkdhbzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICA8L2NyZWF0b3JzPgogIDx0aXRsZXM+CiAgICA8dGl0bGU+RGlzcnVwdGlvbiBvZiBCUkQ0IGF0IEgzSzI3QWMtZW5yaWNoZWQgZW5oYW5jZXIgcmVnaW9uIGNvcnJlbGF0ZXMgd2l0aCBkZWNyZWFzZWQgYy1NeWMgZXhwcmVzc2lvbiBpbiBNZXJrZWwgY2VsbCBjYXJjaW5vbWE8L3RpdGxlPgogIDwvdGl0bGVzPgogIDxkZXNjcmlwdGlvbnM+CiAgICA8ZGVzY3JpcHRpb24gZGVzY3JpcHRpb25UeXBlPSJBYnN0cmFjdCI+Jmx0O2RpdiZndDsmbHQ7cCZndDtQYXRob2xvZ2ljIGMtTXljIGV4cHJlc3Npb24gaXMgZnJlcXVlbnRseSBkZXRlY3RlZCBpbiBodW1hbiBjYW5jZXJzLCBpbmNsdWRpbmcgTWVya2VsIGNlbGwgY2FyY2lub21hIChNQ0MpLCBhbiBhZ2dyZXNzaXZlIHNraW4gY2FuY2VyIHdpdGggbm8gY3VyZSBmb3IgbWV0YXN0YXRpYyBkaXNlYXNlLiBCcm9tb2RvbWFpbiBwcm90ZWluIDQgKEJSRDQpIHJlZ3VsYXRlcyBnZW5lIHRyYW5zY3JpcHRpb24gYnkgYmluZGluZyB0byBhY2V0eWxhdGVkIGhpc3RvbmUgSDMgbHlzaW5lIDI3IChIM0syN0FjKSBvbiB0aGUgY2hyb21hdGluLiBTdXBlci1lbmhhbmNlcnMgb2YgdHJhbnNjcmlwdGlvbiBhcmUgaWRlbnRpZmllZCBieSBlbnJpY2htZW50IG9mIEgzSzI3QWMuIEJFVCBpbmhpYml0b3IgSlExIGRpc3J1cHRzIEJSRDQgYXNzb2NpYXRpb24gd2l0aCBzdXBlci1lbmhhbmNlcnMsIGRvd25yZWd1bGF0ZXMgcHJvdG8tb25jb2dlbmVzLCBzdWNoIGFzICZsdDtpJmd0O2MtTXljJmx0Oy9pJmd0OywgYW5kIGRpc3BsYXlzIGFudGl0dW1vciBhY3Rpdml0eSBpbiBwcmVjbGluaWNhbCBhbmltYWwgbW9kZWxzIG9mIGh1bWFuIGNhbmNlcnMuIEhlcmUgd2Ugc2hvdyB0aGF0IGFuIGVuaGFuY2VyIHByb3hpbWFsIHRvIHRoZSAmbHQ7aSZndDtjLU15YyZsdDsvaSZndDsgcHJvbW90ZXIgaXMgZW5yaWNoZWQgaW4gSDNLMjdBYyBhbmQgYXNzb2NpYXRlZCB3aXRoIGhpZ2ggb2NjdXBhbmN5IG9mIEJSRDQsIGFuZCBjb2luY2lkZXMgd2l0aCBhIHB1dGF0aXZlICZsdDtpJmd0O2MtTXljJmx0Oy9pJmd0OyBzdXBlci1lbmhhbmNlciBpbiBNQ0MgY2VsbHMuIFRoaXMgb2JzZXJ2YXRpb24gaXMgbWlycm9yZWQgaW4gdHVtb3JzIGZyb20gTUNDIHBhdGllbnRzLiBJbXBvcnRhbnRseSwgZGVwbGV0ZWQgQlJENCBvY2N1cGFuY3kgYXQgdGhlIHB1dGF0aXZlICZsdDtpJmd0O2MtTXljJmx0Oy9pJmd0OyBzdXBlci1lbmhhbmNlciByZWdpb24gYnkgSlExIGNvcnJlbGF0ZXMgd2l0aCBkZWNyZWFzZWQgYy1NeWMgZXhwcmVzc2lvbi4gVGh1cywgb3VyIHN0dWR5IHByb3ZpZGVzIGluaXRpYWwgZXZpZGVuY2UgdGhhdCBzdXBlci1lbmhhbmNlcnMgcmVndWxhdGUgYy1NeWMgZXhwcmVzc2lvbiBpbiBNQ0MuJmx0Oy9wJmd0OyZsdDsvZGl2Jmd0OzwvZGVzY3JpcHRpb24+CiAgPC9kZXNjcmlwdGlvbnM+CiAgPHN1YmplY3RzPgogICAgPHN1YmplY3Q+SW5mZWN0aW91cyBEaXNlYXNlczwvc3ViamVjdD4KICAgIDxzdWJqZWN0PkhlbWF0b2xvZ3k8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DYW5jZXI8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5EZXZlbG9wbWVudGFsIEJpb2xvZ3k8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5CaW9sb2dpY2FsIFNjaWVuY2VzPC9zdWJqZWN0PgogICAgPHN1YmplY3Q+SW1tdW5vbG9neTwvc3ViamVjdD4KICAgIDxzdWJqZWN0Pk5ldXJvc2NpZW5jZTwvc3ViamVjdD4KICAgIDxzdWJqZWN0Pk1vbGVjdWxhciBCaW9sb2d5PC9zdWJqZWN0PgogICAgPHN1YmplY3Q+R2VuZXRpY3M8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DZWxsIEJpb2xvZ3k8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5CaW9jaGVtaXN0cnk8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5CaW9waHlzaWNzPC9zdWJqZWN0PgogIDwvc3ViamVjdHM+CiAgPHB1Ymxpc2hlcj5UYXlsb3IgJmFtcDsgRnJhbmNpczwvcHVibGlzaGVyPgogIDxwdWJsaWNhdGlvblllYXI+MjAxNTw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