Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance

Akihiko Numata, Hui Si Kwok, Qi Ling Zhou, Jia Li, Roberto Tirado-Magallanes, Vladimir Espinosa Angarica, Rebecca Hannah, Jihye Park, Chelsia Qiuxia Wang, Vaidehi Krishnan, Deepa Rajagopalan, Yanzhou Zhang, Siqin Zhou, Robert S. Welner, Motomi Osato, Sudhakar Jha, Stefan K. Bohlander, Berthold Göttgens, Henry Yang, Touati BenoukrafJohn W. Lough, Deepak Bararia, Daniel G. Tenen

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1735-1747
Number of pages13
JournalBlood
Volume136
Issue number15
DOIs
Publication statusPublished - Oct 8 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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