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dc.contributor.authorGarcia-Carpizo, Veronica
dc.contributor.authorRuiz-Llorente, Sergio
dc.contributor.authorSarmentero, Jacinto
dc.contributor.authorGraña Castro, Osvaldo 
dc.contributor.authorPisano, David G
dc.contributor.authorBarrero, Maria Jose 
dc.date.accessioned2018-12-12T12:02:52Z
dc.date.available2018-12-12T12:02:52Z
dc.date.issued2018
dc.identifier.citationEpigenetics Chromatin. 2018;11(1):30.es_ES
dc.identifier.issn1756-8935es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6821
dc.description.abstractBACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy. In accordance, CREBBP/EP300 bromodomain inhibitors interfere with GATA1- and MYC-driven transcription, causing the accumulation of cells in the G0/G1 phase of the cell cycle. The CREBBP/CBP30 bromodomain inhibitor CBP30 displaces CREBBP and EP300 from GATA1 and MYC binding sites at enhancers, resulting in a decrease in the levels of histone acetylation at these regulatory regions and consequently reduced gene expression of critical genes controlled by these transcription factors. CONCLUSIONS: Our data shows that inhibition of CREBBP/EP300 bromodomains can interfere with oncogene-driven transcriptional programs in cancer cells and consequently hold therapeutic potential.es_ES
dc.description.sponsorshipWe thank M. Serrano for critical reading of the manuscript. A‑485 was a gift from the Structural Genomics Consortium. We also thank the Flow Cytometry and Genomics Units at the CNIO.es_ES
dc.language.isoenges_ES
dc.publisherBioMed Central (BMC) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBromodomainses_ES
dc.subjectCanceres_ES
dc.subjectEpigeneticses_ES
dc.subjectProliferationes_ES
dc.subject.meshCREB-Binding Protein es_ES
dc.subject.meshCell Cycle es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshE1A-Associated p300 Protein es_ES
dc.subject.meshEnhancer Elements, Genetices_ES
dc.subject.meshGATA1 Transcription Factor es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshHumans es_ES
dc.subject.meshK562 Cells es_ES
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive es_ES
dc.subject.meshProtein Domains es_ES
dc.subject.meshProto-Oncogene Proteins c-myc es_ES
dc.subject.meshTranscription, Genetices_ES
dc.titleCREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferationes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29884215es_ES
dc.format.volume11es_ES
dc.format.number1es_ES
dc.format.page30es_ES
dc.identifier.doi10.1186/s13072-018-0197-xes_ES
dc.contributor.funderFundación Lilly 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1756-8935es_ES
dc.relation.publisherversionhttps://doi.org/10.1186/s13072-018-0197-x.es_ES
dc.identifier.journalEpigenetics & chromatines_ES
dc.repisalud.institucionCNIOes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional