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- Title
MOZ-Mediated Repression of p16<sup>INK</sup><sup>4</sup><sup>a</sup> Is Critical for the Self-Renewal of Neural and Hematopoietic Stem Cells.
- Authors
Perez-Campo, Flor M.; Costa, Guilherme; Lie-a-Ling, Michael; Stifani, Stefano; Kouskoff, Valerie; Lacaud, Georges
- Abstract
Although inhibition of p16INK4a expression is critical to preserve the proliferative capacity of stem cells, the molecular mechanisms responsible for silencing p16INK4a expression remain poorly characterized. Here, we show that the histone acetyltransferase (HAT) monocytic leukemia zinc finger protein (MOZ) controls the proliferation of both hematopoietic and neural stem cells by modulating the transcriptional repression of p16INK4a. In the absence of the HAT activity of MOZ, expression of p16INK4a is upregulated in progenitor and stem cells, inducing an early entrance into replicative senescence. Genetic deletion of p16INK4a reverses the proliferative defect in both MozHAT−/− hematopoietic and neural progenitors. Our results suggest a critical requirement for MOZ HAT activity to silence p16INK4a expression and to protect stem cells from early entrance into replicative senescence. S tem C ells 2014;32:1591-1601
- Subjects
MONOCYTIC leukemia; ZINC-finger proteins; HEMATOPOIETIC stem cells; CYCLIN-dependent kinase inhibitors; GENE expression; CELL proliferation; GENE silencing; HISTONE acetyltransferase; NEURAL stem cells
- Publication
Stem Cells, 2014, Vol 32, Issue 6, p1591
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1606