TY - JOUR
T1 - Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus
AU - Watanabe, Toshiaki
AU - Tomizawa, Shin Ichi
AU - Mitsuya, Kohzoh
AU - Totoki, Yasushi
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
Y1 - 2011/5/13
N2 - 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.
AB - 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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U2 - 10.1126/science.1203919
DO - 10.1126/science.1203919
M3 - Article
C2 - 21566194
AN - SCOPUS:79956052873
SN - 0036-8075
VL - 332
SP - 848
EP - 852
JO - Science
JF - Science
IS - 6031
ER -