dc.creator | Okuda, Hiroshi | |
dc.creator | Stanojević, Boban | |
dc.creator | Kanai, Akinori | |
dc.creator | Kawamura, Takeshi | |
dc.creator | Takahashi, Satoshi | |
dc.creator | Matsui, Hirotaka | |
dc.creator | Takaori-Kondo, Akifumi | |
dc.creator | Yokoyama, Akihiko | |
dc.date.accessioned | 2018-03-01T17:34:24Z | |
dc.date.available | 2018-03-01T17:34:24Z | |
dc.date.issued | 2017 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.issn | 1558-8238 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/1538 | |
dc.description.abstract | The 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.relation | Japan Society for the Promotion of Science (JSPS) KAKENHI [16H05337] | |
dc.relation | Dainippon Sumitomo Pharma Co. Ltd. | |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Journal of Clinical Investigation | en |
dc.title | Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia | en |
dc.type | article | en |
dc.rights.license | BY | |
dcterms.abstract | Такаори-Кондо, Aкифуми; Станојевић Бобан; Yокоyама, Aкихико; Окуда, Хиросхи; Каwамура, Такесхи; Канаи, Aкинори; Такахасхи, Сатосхи; Матсуи, Хиротака; | |
dc.citation.volume | 127 | |
dc.citation.issue | 5 | |
dc.citation.spage | 1918 | |
dc.citation.epage | 1931 | |
dc.identifier.wos | 000400381000030 | |
dc.identifier.doi | 10.1172/JCI91406 | |
dc.citation.rank | aM21 | |
dc.identifier.pmid | 28394257 | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-85018955347 | |
dc.identifier.fulltext | https://vinar.vin.bg.ac.rs//bitstream/id/11904/1534.pdf | |