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dc.creatorOkuda, Hiroshi
dc.creatorStanojević, Boban
dc.creatorKanai, Akinori
dc.creatorKawamura, Takeshi
dc.creatorTakahashi, Satoshi
dc.creatorMatsui, Hirotaka
dc.creatorTakaori-Kondo, Akifumi
dc.creatorYokoyama, Akihiko
dc.date.accessioned2018-03-01T17:34:24Z
dc.date.available2018-03-01T17:34:24Z
dc.date.issued2017
dc.identifier.issn0021-9738 (print)
dc.identifier.issn1558-8238 (electronic)
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/1538
dc.description.abstractThe eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4-ENL-P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia.en
dc.relationJapan Society for the Promotion of Science (JSPS) KAKENHI [16H05337], Dainippon Sumitomo Pharma Co., Ltd.
dc.rightsopenAccessen
dc.sourceJournal of Clinical Investigationen
dc.titleCooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemiaen
dc.typearticleen
dcterms.abstractТакаори-Кондо, Aкифуми; Станојевић Бобан; Yокоyама, Aкихико; Окуда, Хиросхи; Каwамура, Такесхи; Канаи, Aкинори; Такахасхи, Сатосхи; Матсуи, Хиротака;
dc.citation.volume127
dc.citation.issue5
dc.citation.spage1918
dc.citation.epage1931
dc.identifier.wos000400381000030
dc.identifier.doi10.1172/JCI91406
dc.identifier.pmid28394257
dc.identifier.scopus2-s2.0-85018955347
dc.identifier.fulltexthttp://vinar.vin.bg.ac.rs//bitstream/id/11904/1534.pdf


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