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Role for piRNA and target non-coding RNA in genomic imprinting

 Press Release 

Science 13 May 2011 

 Sasaki Laboratory (Division of Human Genetics) (Present: Division of Epigenomics, Medical Institute of Bioregulation, Kyushu University)
Fujiyama Laboratory (Comparative Genomics Laboratory, National Institute of Genetics)

 Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.
Toshiaki Watanabe, Shinichi 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 and Hiroyuki Sasaki.
Science 332,848-852. 2011. DOI:10.1126/science.1203919

  Genomic imprinting causes parental-origin-specific monoallelic gene expression through differential DNA methylation established in the parental germline. Imprinting is essential for normal mammalian development, and its aberration can cause malformation syndromes and tumors. The mechanisms underlying how specific sequences are selectively methylated in the germline are not fully understood. We have found that the PIWI-interacting RNA (piRNA) pathway, which essentially silences retrotransposons, is required for de novo DNA methylation of the imprinting center (differentially methylated region or DMR) of the mouse Rasgrf1 locus, but not other paternally imprinted loci. A retrotransposon sequence within a non-coding 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 its target RNA direct the sequence-specific methylation of Rasgrf1.

The piRNA pathway has been known to silence transposons in the germline. Our study reveals that this system is essential for de novo DNA methylation and imprinting of the mouse Rasgrf1 locus, which controls post-natal growth.