title: Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.
abstract: Genomic imprinting causes parental origin-specific monoallelic gene expression through differential DNA methylation established in the parental germ line. However, the mechanisms underlying how specific sequences are selectively methylated are not fully understood. We have found that the components of the PIWI-interacting RNA (piRNA) pathway are required for de novo methylation of the differentially methylated region (DMR) of the imprinted mouse Rasgrf1 locus, but not other paternally imprinted loci. A retrotransposon sequence within a noncoding RNA spanning the DMR was targeted by piRNAs generated from a different locus. A direct repeat in the DMR, which is required for the methylation and imprinting of Rasgrf1, served as a promoter for this RNA. We propose a model in which piRNAs and a target RNA direct the sequence-specific methylation of Rasgrf1.
authors.affiliation: Division of Human Genetics and Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, 411-8540, Japan. toshwatatoshiakiwatanabe@gmail.com
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tomizawa
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Mitsuya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Totoki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Kuramochi-Miyagawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Iida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hoki
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Murphy
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Kengo
authors.initials: K
authors.lastname: Gotoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hiura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arima
authors.forename: Asao
authors.initials: A
authors.lastname: Fujiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Sado
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Haifan
authors.initials: H
authors.lastname: Lin
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichiyanagi
authors.forename: Paul D
authors.initials: PD
authors.lastname: Soloway
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D019175:DNA Methylation; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements; D013093:Spermatogonia / Q000378:metabolism; D013737:Testis / Q000196:embryology / Q000378:metabolism; D014158:Transcription, Genetic; D020666:ras-GRF1 / Q000235:genetics*
chemical_list: D060565:Argonaute Proteins; D024101:Mitochondrial Proteins; C448522:Piwil1 protein, mouse; C448521:Piwil2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; C513037:Rasgrf1 protein, mouse; D018626:Retroelements; D020666:ras-GRF1; D010739:Phospholipase D; C558126:mitoPLD protein, mouse