MOZ-Mediated Repression of p16 super(INK4a) Is Critical for the Self-Renewal of Neural and Hematopoietic Stem Cells

Although inhibition of p16 super(INK4a) expression is critical to preserve the proliferative capacity of stem cells, the molecular mechanisms responsible for silencing p16 super(INK4a) expression remain poorly characterized. Here, we show that the histone acetyltransferase (HAT) monocytic leukemia z...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2014-06, Vol.32 (6), p.1591-1601
Main Authors: Perez-Campo, Flor M, Costa, Guilherme, Lie-a-Ling, Michael, Stifani, Stefano, Kouskoff, Valerie, Lacaud, Georges
Format: Article
Language:English
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Summary:Although inhibition of p16 super(INK4a) expression is critical to preserve the proliferative capacity of stem cells, the molecular mechanisms responsible for silencing p16 super(INK4a) 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 p16 super(INK4a). In the absence of the HAT activity of MOZ, expression of p16 super(INK4a) is upregulated in progenitor and stem cells, inducing an early entrance into replicative senescence. Genetic deletion of p16 super(INK4a) reverses the proliferative defect in both Moz super(HAT-/-) hematopoietic and neural progenitors. Our results suggest a critical requirement for MOZ HAT activity to silence p16 super(INK4a) expression and to protect stem cells from early entrance into replicative senescence. Stem Cells 2014; 32:1591-1601
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1606