title: MORC1 represses transposable elements in the mouse male germline.
abstract: The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. MORC1-deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Pastor
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: Hume
authors.initials: H
authors.lastname: Stroud
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Nee
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Liu
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Pezic
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Manakov
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: Serena A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moissiard
authors.affiliation: Unité de génétique et biologie du développement, Instititute Curie, CNRS UMR3215, INSERM U934, Paris 75005, France.
authors.forename: Natasha
authors.initials: N
authors.lastname: Zamudio
authors.affiliation: Unité de génétique et biologie du développement, Instititute Curie, CNRS UMR3215, INSERM U934, Paris 75005, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Bourc'his
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Aravin
authors.affiliation: 1] Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA [2] Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, USA.
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
authors.affiliation: 1] Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, 4028 Terasaki Life Sciences Building, 610 Charles E. Young Drive East, Los Angeles, California 90095, USA [2] Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, USA [3] Howard Hughes Medical Institute, University of California Los Angeles, 675 Charles E. Young Drive South, Los Angeles, California 90095, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements; D004622:Embryo, Mammalian; D044127:Epigenesis, Genetic; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004251:DNA Transposable Elements; C120546:Morc1 protein, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases