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MOZ‐Mediated Repression of p16INK4a Is Critical for the Self‐Renewal of Neural and Hematopoietic Stem Cells
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. Stem Cells 2014;32:1591–1601
Citing Literature
Number of times cited according to CrossRef: 25
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