Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus |
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Authors: | Watanabe Toshiaki Tomizawa Shin-ichi Mitsuya Kohzoh Totoki Yasushi Yamamoto Yasuhiro Kuramochi-Miyagawa Satomi Iida Naoko 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 |
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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 |
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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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