Journal
SCIENCE
Volume 332, Issue 6031, Pages 848-852Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1203919
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grants-in-Aid for Scientific Research [21115005, 21200037, 23710223, 20062010, 21115006, 22770009, 23013003, 19061001, 23390385, 23659768] Funding Source: KAKEN
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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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