title: Two waves of de novo methylation during mouse germ cell development.
abstract: During development, mammalian germ cells reprogram their epigenomes via a genome-wide erasure and de novo rewriting of DNA methylation marks. We know little of how methylation patterns are specifically determined. The piRNA pathway is thought to target the bulk of retrotransposon methylation. Here we show that most retrotransposon sequences are modified by default de novo methylation. However, potentially active retrotransposon copies evade this initial wave, likely mimicking features of protein-coding genes. These elements remain transcriptionally active and become targets of piRNA-mediated methylation. Thus, we posit that these two waves play essential roles in resetting germ cell epigenomes at each generation.
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Antoine
authors.initials: A
authors.lastname: Molaro
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Ilaria
authors.initials: I
authors.lastname: Falciatori
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Emily
authors.initials: E
authors.lastname: Hodges
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Aravin
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Krista
authors.initials: K
authors.lastname: Marran
authors.affiliation: Ansary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA;
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: W Richard
authors.initials: WR
authors.lastname: McCombie
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D008297:Male; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D018626:Retroelements / Q000235:genetics*; D013090:Spermatocytes / Q000166:cytology* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D034741:RNA, Small Interfering; D018626:Retroelements
keywords: DNA methylation; LINE; LTR; germ cells; piRNA; retrotransposon