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

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    237 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 - May 13 2011

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    All Science Journal Classification (ASJC) codes

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    Cite this

    Watanabe, T., Tomizawa, S. I., Mitsuya, K., Totoki, Y., Yamamoto, Y., Kuramochi-Miyagawa, S., ... Sasaki, H. (2011). Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science, 332(6031), 848-852. https://doi.org/10.1126/science.1203919