Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus

Toshiaki Watanabe, Shin Ichi Tomizawa, Kohzoh Mitsuya, Yasushi Totoki, Yasuhiro Yamamoto, Satomi Kuramochi-Miyagawa, Naoko Iida, Yuko Hoki, Patrick J. Murphy, Atsushi Toyoda, Kengo Gotoh, Hitoshi Hiura, Takahiro Arima, Asao Fujiyama, Takashi Sado, Tatsuhiro Shibata, Toru Nakano, Haifan Lin, Kenji Ichiyanagi, Paul D. SolowayHiroyuki Sasaki

Research output: Contribution to journalArticlepeer-review

275 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)848-852
Number of pages5
JournalScience
Volume332
Issue number6031
DOIs
Publication statusPublished - 2011 May 13

ASJC Scopus subject areas

  • General

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