
Genomic imprinting is an epigenetic phenomenon that causes parent-of-origin specific monoallelic expression of a specific set of genes in mammals. Imprinting has crucial influences on embryonic growth, placental development, and animal behavior. It is known that monoallelic expression of the imprinted genes is regulated by differential DNA methylation established during male and female gametogenesis. However, little is known about the mechanisms underlying the target specific de novo DNA methylation and imprinting in germ cells. We have recently found that the piRNA system is involved in de novo DNA methylation of mouse Rasgrf1 , a paternally methylated imprinted locus, in prospermatogonia of the fetal testis. The piRNA system has been known to silence retrotransposons in germ cells, but our case provides the first evidence that a protein-coding gene is regulated by this system. Based on the findings, we propose a mechanistic model in which the specificity of de novo DNA methylation is determined by the interaction between piRNAs and nascent RNAs transcribed at the target regions.
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