title: SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination.
abstract: Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells.
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Ho-Su
authors.initials: HS
authors.lastname: Sin
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: So
authors.initials: S
authors.lastname: Maezawa
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Broering
authors.affiliation: Division of Allergy and Immunology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kartashov
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Kris G
authors.initials: KG
authors.lastname: Alavattam
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ichijima
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Allergy and Immunology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: W Clark
authors.initials: WC
authors.lastname: Bacon
authors.affiliation: Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Greis
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Andreassen
authors.affiliation: Division of Allergy and Immunology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA.
authors.forename: Artem
authors.initials: A
authors.lastname: Barski
authors.affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 49267, USA. Electronic address: satoshi.namekawa@cchmc.org.
authors.forename: Satoshi H
authors.initials: SH
authors.lastname: Namekawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone; D057890:Epigenomics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005854:Germ Cells; D006657:Histones / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012730:Sex Chromosomes / Q000235:genetics; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C462180:Dppa3 protein, mouse; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C508937:MDC1 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D025801:Ubiquitin; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases