Journal
CELL STEM CELL
Volume 11, Issue 5, Pages 649-662Publisher
CELL PRESS
DOI: 10.1016/j.stem.2012.08.001
Keywords
-
Categories
Funding
- Human Frontiers Science Program Organization
- Spanish Ministries of Science and Innovation and Health [SAF2010-15386, FIS PI06/0627]
- Ministerio de Economia y Competitividad
- Pro-CNIC Foundation
Ask authors/readers for more resources
Polycomb group (PcG) proteins are key epigenetic regulators of hematopietic stem cell (HSC) fate. The PcG members Ezh2 and Ezh2 are important determinants of embryonic stem cell identity, and the transcript levels of these histone methyltransferases are inversely correlated during development. However, the role of Ezh1 in somatic stem cells is largely unknown. Here we show that Ezh1 maintains repopulating HSCs in a slow-cycling, undifferentiated state, protecting them from senescence. Ezh1 ablation induces significant loss of adult HSCs, with concomitant impairment of their self-renewal capacity due to a potent senescence response. Epigenomic and gene expression changes induced by Ezh1 deletion in senesced HSCs demonstrated that Ezh1-mediated PRC2 activity catalyzes monomethylation and dimethylation of H3K27. Deletion of Cdkn2a on the Ezh1 null background rescued HSC proliferation and survival. Our results suggest that Ezh1 is an important histone methyltransferase for HSC maintenance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available