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

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1735-1747
ページ数13
ジャーナルBlood
136
15
DOI
出版ステータス出版済み - 10 8 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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