MOZ-mediated repression of p16(INK) (4) (a) is critical for the self-renewal of neural and hematopoietic stem cells.

Flor M. Perez-Campo, Guilherme Costa, Michael Lie-A-Ling, Stefano Stifani, Valerie Kouskoff, Georges Lacaud

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1591-1601
Number of pages11
JournalStem Cells
Volume32
Issue number6
DOIs
Publication statusPublished - 01 Jun 2014

Bibliographical note

, Biotechnology and Biological Sciences Research Council, United Kingdom, Cancer Research UK, United Kingdom

Keywords

  • Epigenetics
  • Hematopoietic stem cell
  • Histone acetylation
  • MOZ
  • Neural stem cells
  • Senescence

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