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Background    Rasgrf1  is imprinted in mouse, displaying paternal allele specific expression in neonatal brain. Paternal expression is accompanied by paternal-specific DNA methylation at a differentially methylated domain (DMD) within the locus. The  cis -acting elements necessary for  Rasgrf1  imprinting are known. A series of tandem DNA repeats control methylation of the adjacent DMD, which is a methylation sensitive enhancer-blocking element. These two sequences constitute a binary switch that controls imprinting and represents the Imprinting Control Region (ICR). One paternally transmitted mutation, which helped define the ICR, induced paramutation, in  trans , on the maternal allele. Like many imprinted genes,  Rasgrf1  lies within an imprinted cluster. One of four noncoding transcripts in the cluster,  AK015891 , is known to be imprinted.    Methodology/Principal Findings  Here we demonstrate that an additional noncoding RNA,  AK029869 , is imprinted and paternally expressed in brain throughout development. Intriguingly, any of several maternally inherited ICR mutations affected expression of the paternal  AK029869  transcript in  trans . Furthermore, we found that the ICR mutations exert different  trans  effects on  AK029869  at different developmental times.    Conclusions/Significance  Few  trans  effects have been defined in mammals and, those that exist, do not show the great variation seen at the  Rasgrf1  imprinted domain, either in terms of the large number of mutations that produce the effects or the range of phenotypes that emerge when they are seen. These results suggest that  trans  regulation of gene expression may be more common than originally appreciated and that where  trans  regulation occurs it can change dynamically during development.

A Non-Coding RNA Within the Rasgrf1 Locus in Mouse Is Imprinted and Regulated by Its Homologous Chromosome in Trans