| Literature DB >> 32542325 |
Akihiko Numata1,2, Hui Si Kwok1, Qi-Ling Zhou1, Jia Li1, Roberto Tirado-Magallanes1, Vladimir Espinosa Angarica1, Rebecca Hannah3,4, Jihye Park5, Chelsia Qiuxia Wang1, Vaidehi Krishnan1, Deepa Rajagopalan1, Yanzhou Zhang1, Siqin Zhou1, Robert S Welner6, Motomi Osato1, Sudhakar Jha1, Stefan K Bohlander7, Berthold Göttgens3,4, Henry Yang1, Touati Benoukraf1,8, John W Lough9, Deepak Bararia1,10, Daniel G Tenen1,10.
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.Entities:
Mesh：
Substances：
Year: 2020 PMID： 32542325 PMCID： PMC7544546 DOI： 10.1182/blood.2019001279
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113