期刊
GENES & DEVELOPMENT
卷 22, 期 24, 页码 3403-3408出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1741408
关键词
Chromatin; epigenetic; genome-wide; leukemia; stem cell; transcription
资金
- Israel Cancer Research Fund
- Wolfson Foundation
- US-Israel BSF
- NIH [CA 128609, HG002668]
- NHLBI [F32HL082448]
Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer.
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