a non-coding rna within the rasgrf1 locus in mouse is imprinted and regulated by its homologous chromosome in trans非编码rna在rasgrf1鼠标轨迹是印在反式和由其同源染色体.pdfVIP

A Non-Coding RNA Within the Rasgrf1 Locus in Mouse Is Imprinted and Regulated by Its Homologous Chromosome in Trans Chelsea M. Brideau., Krista P. Kauppinen., Rebecca Holmes, Paul D. Soloway* Division of Nutritional Sciences, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America Abstract 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 t