Journal
GENES & DEVELOPMENT
Volume 26, Issue 4, Pages 344-349Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.184341.111
Keywords
DNA methylation; leukemia stem cell; Dnmt1; bivalent chromatin
Categories
Funding
- Leukemia and Lymphoma Society
- Children's Leukemia Research Foundation
- ASH
- NIH [CA105423]
- GO [CA148222]
- HSCI
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Epigenetic mechanisms regulating leukemia stem cells (LSCs) are an attractive target for therapy of blood cancers. Here, we report that conditional knockout of the DNA methyltransferase Dnmt1 blocked development of leukemia, and haploinsufficiency of Dnmt1 was sufficient to delay progression of leukemogenesis and impair LSC self-renewal without altering normal hematopoiesis. Haploinsufficiency of Dnmt1 resulted in tumor suppressor gene derepression associated with reduced DNA methylation and bivalent chromatin marks. These results suggest that LSCs depend on not only active expression of leukemogenic programs, but also DNA methylation-mediated silencing of bivalent domains to enforce transcriptional repression.
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