Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance
- 8 October 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (15), 1735-1747
- https://doi.org/10.1182/blood.2019001279
Abstract
Hematopoietic stem cells (HSC) have the potential to replenish the blood system for the lifetime of the organism. Their two defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Here, using conditional gene knockout models, we demonstrate a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance both in the embryonic and adult stages, which depends on its acetyltransferase activity. Genome-wide chromatin and transcriptome profiling in murine hematopoietic stem and progenitor cells revealed that Tip60 co-localizes with c-Myc and that Tip60 deletion suppress the expression of Myc target genes, which are associated with critical biological processes for HSC maintenance, cell-cycle and DNA repair. Notably, acetylated H2A.Z (acH2A.Z) was enriched at the Tip60-bound active chromatin and Tip60 deletion induced a robust reduction in the acH2A.Z / H2A.Z ratio. These results uncover a critical epigenetic regulatory layer for HSC maintenance at least in part through Tip60 dependent H2A.Z acetylation to activate Myc target genes.Keywords
This publication has 57 references indexed in Scilit:
- Acetylation of H2A.Z is a key epigenetic modification associated with gene deregulation and epigenetic remodeling in cancerGenome Research, 2011
- Essential Role of p400/mDomino Chromatin-remodeling ATPase in Bone Marrow Hematopoiesis and Cell-cycle ProgressionJournal of Biological Chemistry, 2010
- Homozygous disruption of the tip60 gene causes early embryonic lethalityDevelopmental Dynamics, 2009
- Acetylation of Vertebrate H2A.Z and Its Effect on the Structure of the NucleosomeBiochemistry, 2009
- Hematopoietic Stem Cell Function and Survival Depend on c-Myc and N-Myc ActivityCell Stem Cell, 2008
- H2AZ Is Enriched at Polycomb Complex Target Genes in ES Cells and Is Necessary for Lineage CommitmentCell, 2008
- Hematopoiesis: An Evolving Paradigm for Stem Cell BiologyCell, 2008
- High-Resolution Profiling of Histone Methylations in the Human GenomeCell, 2007
- MOZ is essential for maintenance of hematopoietic stem cellsGenes & Development, 2006
- Transgenic mice with hematopoietic and lymphoid specific expression of CreEuropean Journal of Immunology, 2003