title: Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest.
abstract: Polycomb group (PcG) proteins are key epigenetic regulators of hematopietic stem cell (HSC) fate. The PcG members Ezh2 and Ezh1 are important determinants of embryonic stem cell identity, and the transcript levels of these histone methyltransferases are inversely correlated during development. However, the role of Ezh1 in somatic stem cells is largely unknown. Here we show that Ezh1 maintains repopulating HSCs in a slow-cycling, undifferentiated state, protecting them from senescence. Ezh1 ablation induces significant loss of adult HSCs, with concomitant impairment of their self-renewal capacity due to a potent senescence response. Epigenomic and gene expression changes induced by Ezh1 deletion in senesced HSCs demonstrated that Ezh1-mediated PRC2 activity catalyzes monomethylation and dimethylation of H3K27. Deletion of Cdkn2a on the Ezh1 null background rescued HSC proliferation and survival. Our results suggest that Ezh1 is an important histone methyltransferase for HSC maintenance.
authors.affiliation: Stem Cell Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), E-28029 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hidalgo
authors.forename: Antonio
authors.initials: A
authors.lastname: Herrera-Merchan
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Ligos
authors.forename: Laura
authors.initials: L
authors.lastname: Carramolino
authors.forename: Javier
authors.initials: J
authors.lastname: Nuñez
authors.forename: Fernando
authors.initials: F
authors.lastname: Martinez
authors.forename: Orlando
authors.initials: O
authors.lastname: Dominguez
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D019942:Genes, p16; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: C498408:Ezh1 protein, mouse; D063151:Polycomb Repressive Complex 2