title: EZH1 in germ cells safeguards the function of PRC2 during spermatogenesis.
abstract: We previously reported the requirement of Polycomb Repressive Complex 2 (PRC2) for spermatogenesis through transcriptional repression of somatic genes and meiosis-specific genes. To characterize how PRC2's two methyltransferase subunits, EZH1 and EZH2, regulate histone H3 lysine 27 (H3K27) methylation during germ cell development, we generated mouse models with a germline ablation of EZH1 and/or EHZ2. Only the combined loss of EZH1 and EZH2 caused a depletion of global H3K27me3 marks and meiotic arrest in spermatocytes. Genome-wide analysis of H3K27me3 in spermatogenic cells revealed that a noncanonical EZH1-PRC2 could establish and maintain this histone mark on somatic genes and certain meiotic genes. Consistent with it having active enhancers in testis, Ezh1 was not only abundant in highly differentiated spermatocytes but also in actively proliferating progenitor and stem germ cells. Taken together, our findings suggest that the expression level of Ezh1 determines the restoration of H3K27 methylation in the absence of the canonical EZH2-PRC2.
authors.affiliation: Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Mu
authors.affiliation: Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Starmer
authors.affiliation: Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
authors.forename: Della
authors.initials: D
authors.lastname: Yee
authors.affiliation: Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA. Electronic address: trm4@med.unc.edu.
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D001483:Base Sequence; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D005298:Fertility; D017353:Gene Deletion; D016678:Genome; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D018345:Mice, Knockout; D008938:Mitosis; D008954:Models, Biological; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: D006657:Histones; D000071221:Enhancer of Zeste Homolog 2 Protein; C498408:Ezh1 protein, mouse; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2; D008239:Lysine
keywords: EZH1; EZH2; Enhancer; Histone methylation; Polycomb-Group protein; Spermatogenesis