Open AccessMOZ‐Mediated Repression of p16 INK 4 a Is Critical for the Self‐Renewal of Neural and Hematopoietic Stem Cells
Author(s) -
PerezCampo Flor M.,
Costa Guilherme,
LieaLing Michael,
Stifani Stefano,
Kouskoff Valerie,
Lacaud Georges
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1606
Subject(s) - biology , neural stem cell , stem cell , progenitor cell , microbiology and biotechnology , haematopoiesis , gene silencing , psychological repression , cancer research , gene expression , genetics , gene
Although inhibition of p16 INK4a expression is critical to preserve the proliferative capacity of stem cells, the molecular mechanisms responsible for silencing p16 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 INK4a . In the absence of the HAT activity of MOZ, expression of p16 INK4a is upregulated in progenitor and stem cells, inducing an early entrance into replicative senescence. Genetic deletion of p16 INK4a reverses the proliferative defect in both Moz HAT − / − hematopoietic and neural progenitors. Our results suggest a critical requirement for MOZ HAT activity to silence p16 INK4a expression and to protect stem cells from early entrance into replicative senescence. S tem C ells 2014;32:1591–1601