Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus

• Published in: Science (American Association for the Advancement of Science) Vol. 332; no. 6031; pp. 848 - 852
• Main Authors: Watanabe, Toshiaki, Tomizawa, Shin-ichi, Mitsuya, Kohzoh, Totoki, Yasushi, Yamamoto, Yasuhiro, Kuramochi-Miyagawa, Satomi, Iida, Naoka, Hoki, Yuko, Murphy, Patrick J., Toyoda, Atsushi, Gotoh, Kengo, Hiura, Hitoshi, Arima, Takahiro, Fujiyama, Asao, Sado, Takashi, Shibata, Tatsuhiro, Nakano, Toru, Lin, Haifan, Ichiyanagi, Kenji, Soloway, Paul D., Sasaki, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 13-05-2011; The American Association for the Advancement of Science
• Subjects: Animals; Argonaute Proteins; Biological and medical sciences; DNA; DNA Methylation; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic loci; Genomic Imprinting; Genomics; Germ cells; Human genetics; Male; Medical genetics; Methylation; Mice; Mice, Inbred C57BL; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Models, Genetic; Molecular and cellular biology; Molecular genetics; Mutation; Phospholipase D - genetics; Phospholipase D - metabolism; Proteins - genetics; Proteins - metabolism; ras-GRF1 - genetics; Repetitive Sequences, Nucleic Acid; Research universities; Retroelements; Retrotransposons; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; Rodents; Spermatogonia - metabolism; Testes; Testis - embryology; Testis - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Vertebrata; Mammalia; Mouse; DNA; Rodentia; Non coding RNA; piRNA; Locus; Methylation; De novo; Genomic imprinting
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1203919

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.