title: Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development.
abstract: Polycomb-repressive complex 2 (PRC2) catalyzes the methylation of histone H3 Lys27 (H3K27) and functions as a critical epigenetic regulator of both stem cell pluripotency and somatic differentiation, but its role in male germ cell development is unknown. Using conditional mutagenesis to remove the core PRC2 subunits EED and SUZ12 during male germ cell development, we identified a requirement for PRC2 in both mitotic and meiotic germ cells. We observed a paucity of mutant spermatogonial stem cells (SSCs), which appears independent of repression of the known cell cycle inhibitors Ink4a/Ink4b/Arf. Moreover, mutant spermatocytes exhibited ectopic expression of somatic lamins and an abnormal distribution of SUN1 proteins on the nuclear envelope. These defects were coincident with abnormal chromosome dynamics, affecting homologous chromosome pairing and synapsis. We observed acquisition of H3K27me3 on stage-specific genes during meiotic progression, indicating a requirement for PRC2 in regulating the meiotic transcriptional program. Together, these data demonstrate that transcriptional repression of soma-specific genes by PRC2 facilitates homeostasis and differentiation during mammalian spermatogenesis.
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Mu
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Starmer
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fedoriw
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Della
authors.initials: D
authors.lastname: Yee
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D007248:Infertility, Male / Q000235:genetics; D034882:Lamins / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000166:cytology*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D034882:Lamins; D063151:Polycomb Repressive Complex 2
keywords: Polycomb group proteins; epigenetic repression; gene expression; meiosis; spermatogenesis; spermatogonia