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

作者：Perez Campo Flor M^*; Costa Guilherme; Lie a Ling Michael; Stifani Stefano; Kouskoff Valerie; Lacaud Georges

来源：Stem Cells, 2014, 32(6): 1591-1601.

DOI：10.1002/stem.1606

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

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.

• 出版日期2014-6