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| Home > Publications database > UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. > print |
| Home > Publications database > UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. > print |
| 001 | 135956 | ||
| 005 | 20240229105048.0 | ||
| 024 | 7 | _ | |a 10.1038/s41588-018-0114-z |2 doi |
| 024 | 7 | _ | |a pmid:29736013 |2 pmid |
| 024 | 7 | _ | |a 1061-4036 |2 ISSN |
| 024 | 7 | _ | |a 1546-1718 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2018-00693 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Gozdecka, Malgorzata |b 0 |
| 245 | _ | _ | |a UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. |
| 260 | _ | _ | |a New York, NY |c 2018 |b Nature America |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1530524026_8467 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss. By integrating proteomic and genomic analyses, we link these changes to UTX regulation of ATP-dependent chromatin remodeling, coordination of the COMPASS complex and enhanced pioneering activity of ETS factors during evolution to AML. Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. |
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| 700 | 1 | _ | |a Meduri, Eshwar |b 1 |
| 700 | 1 | _ | |a Mazan, Milena |b 2 |
| 700 | 1 | _ | |a Tzelepis, Konstantinos |0 0000-0002-4865-7648 |b 3 |
| 700 | 1 | _ | |a Dudek, Monika |b 4 |
| 700 | 1 | _ | |a Knights, Andrew J |b 5 |
| 700 | 1 | _ | |a Pardo, Mercedes |0 0000-0002-3477-9695 |b 6 |
| 700 | 1 | _ | |a Yu, Lu |0 0000-0001-8378-9112 |b 7 |
| 700 | 1 | _ | |a Choudhary, Jyoti S |b 8 |
| 700 | 1 | _ | |a Metzakopian, Emmanouil |b 9 |
| 700 | 1 | _ | |a Iyer, Vivek |b 10 |
| 700 | 1 | _ | |a Yun, Haiyang |b 11 |
| 700 | 1 | _ | |a Park, Naomi |b 12 |
| 700 | 1 | _ | |a Varela, Ignacio |0 0000-0002-0969-506X |b 13 |
| 700 | 1 | _ | |a Bautista, Ruben |b 14 |
| 700 | 1 | _ | |a Collord, Grace |0 0000-0003-1924-4411 |b 15 |
| 700 | 1 | _ | |a Dovey, Oliver |b 16 |
| 700 | 1 | _ | |a Garyfallos, Dimitrios A |b 17 |
| 700 | 1 | _ | |a De Braekeleer, Etienne |b 18 |
| 700 | 1 | _ | |a Kondo, Saki |b 19 |
| 700 | 1 | _ | |a Cooper, Jonathan |b 20 |
| 700 | 1 | _ | |a Göttgens, Berthold |0 0000-0001-6302-5705 |b 21 |
| 700 | 1 | _ | |a Bullinger, Lars |b 22 |
| 700 | 1 | _ | |a Northcott, Paul A |0 P:(DE-HGF)0 |b 23 |
| 700 | 1 | _ | |a Adams, David |b 24 |
| 700 | 1 | _ | |a Vassiliou, George S |0 0000-0003-4337-8022 |b 25 |
| 700 | 1 | _ | |a Huntly, Brian J P |0 0000-0003-0312-161X |b 26 |
| 773 | _ | _ | |a 10.1038/s41588-018-0114-z |g Vol. 50, no. 6, p. 883 - 894 |0 PERI:(DE-600)1494946-5 |n 6 |p 883 - 894 |t Nature genetics |v 50 |y 2018 |x 1546-1718 |
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