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. Soloway; Hiroyuki Sasaki

doi:10.1126/science.1203919

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

Department of Molecular Medicine

Research output: Contribution to journal › Article › peer-review

296 Scopus citations

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 language	English (US)
Pages (from-to)	848-852
Number of pages	5
Journal	Science
Volume	332
Issue number	6031
DOIs	https://doi.org/10.1126/science.1203919
State	Published - May 13 2011

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Watanabe, T., Tomizawa, S. I., Mitsuya, K., Totoki, Y., Yamamoto, Y., Kuramochi-Miyagawa, S., Iida, N., Hoki, Y., Murphy, P. J., Toyoda, A., Gotoh, K., Hiura, H., Arima, T., Fujiyama, A., Sado, T., Shibata, T., Nakano, T., Lin, H., Ichiyanagi, K., ... 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

Watanabe, T, Tomizawa, SI, Mitsuya, K, Totoki, Y, Yamamoto, Y, Kuramochi-Miyagawa, S, Iida, N, Hoki, Y, Murphy, PJ, Toyoda, A, Gotoh, K, Hiura, H, Arima, T, Fujiyama, A, Sado, T, Shibata, T, Nakano, T, Lin, H, Ichiyanagi, K, Soloway, PD & Sasaki, H 2011, 'Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus', Science, vol. 332, no. 6031, pp. 848-852. https://doi.org/10.1126/science.1203919

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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.",

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AU - Watanabe, Toshiaki

AU - Tomizawa, Shin Ichi

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AU - Yamamoto, Yasuhiro

AU - Kuramochi-Miyagawa, Satomi

AU - Iida, Naoko

AU - Hoki, Yuko

AU - Murphy, Patrick J.

AU - Toyoda, Atsushi

AU - Gotoh, Kengo

AU - Hiura, Hitoshi

AU - Arima, Takahiro

AU - Fujiyama, Asao

AU - Sado, Takashi

AU - Shibata, Tatsuhiro

AU - Nakano, Toru

AU - Lin, Haifan

AU - Ichiyanagi, Kenji

AU - Soloway, Paul D.

AU - Sasaki, Hiroyuki

PY - 2011/5/13

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

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