| http://purl.uniprot.org/citations/27733359 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27733359 | http://www.w3.org/2000/01/rdf-schema#comment | "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 vivo Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for CREBBP-mutant lymphomas.SignificanceOur findings establish the tumor suppressor function of CREBBP in GC lymphomas in which CREBBP mutations disable acetylation and result in unopposed deacetylation by BCL6/SMRT/HDAC3 complexes at enhancers of B-cell signaling and immune response genes. Hence, inhibition of HDAC3 can restore the enhancer histone acetylation and may serve as a targeted therapy for CREBBP-mutant lymphomas. Cancer Discov; 7(1); 38-53. ©2016 AACR.See related commentary by Höpken, p. 14This article is highlighted in the In This Issue feature, p. 1."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-16-0975"xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Jiang Y."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Sharma S."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Hiebert S.W."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Wang S."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Roeder R.G."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Geng H."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Tam W."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Gascoyne R.D."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Elemento O."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Hatzi K."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Scott D.W."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Meydan C."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Chu C.S."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Wendel H.G."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Teater M."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Kranz J.E."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Shaknovich R."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Stengel K.R."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Melnick A.M."xsd:string |
| http://purl.uniprot.org/citations/27733359 | http://purl.uniprot.org/core/author | "Ying H.Y."xsd:string |