{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jiang Y"],"funding":["NCI NIH HHS"],"pagination":["38-53"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5300005"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in viv"],"journal":["Cancer discovery"],"pubmed_title":["CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas."],"pmcid":["PMC5300005"],"funding_grant_id":["R01 CA164605","R01 CA187109","R01 CA190384","P01 CA023766","P30 CA008748","R01 CA183876","R01 CA194547","R01 CA178765","T32 CA009582","P50 CA192937"],"pubmed_authors":["Melnick AM","Doane AS","Chu CS","Ennishi D","Roeder RG","McNally D","Teater M","Holson E","Wang L","Jiang Y","Ortega-Molina A","Wang S","Scott DW","Gascoyne RD","Ying HY","Kranz JE","Wendel HG","Sharma S","Elemento O","Meydan C","Agirre X","Li Z","Geng H","Young JW","Parsa S","Hatzi K","Stengel KR","Tam W","Poloway D","Shaknovich R","Hiebert SW"],"additional_accession":[]},"is_claimable":false,"name":"CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas.","description":"Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in viv","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jan","modification":"2026-04-17T15:23:39.501Z","creation":"2019-03-27T02:36:11Z"},"accession":"S-EPMC5300005","cross_references":{"pubmed":["27733359"],"doi":["10.1158/2159-8290.CD-16-0975","10.1158/2159-8290.cd-16-0975"]}}