Repository logo

Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance.

Accepted version

Change log


Numata, Akihiko 
Kwok, Hui Si 
Zhou, Qi-Ling 
Li, Jia 
Tirado-Magallanes, Roberto 


Hematopoietic stem cells (HSCs) have the potential to replenish the blood system for the lifetime of the organism. Their 2 defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Using conditional gene-knockout models, we demonstrated a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance in both 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 colocalizes 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 cycling, 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.



Animals, Biomarkers, Cell Cycle, Cell Differentiation, Cell Self Renewal, DNA Damage, Gene Expression Profiling, Gene Expression Regulation, Hematopoietic Stem Cells, Histones, Lysine Acetyltransferase 5, Mice, Protein Transport, Trans-Activators

Journal Title


Conference Name

Journal ISSN


Volume Title



American Society of Hematology


All rights reserved
Cancer Research UK (21762)
Wellcome Trust (206328/Z/17/Z)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Cancer Research UK, Wellcome Trust, National Institutes of Health, Singapore state funding