title: Epigenome-wide analysis of piRNAs in gene-specific DNA methylation.
abstract: PIWI-interacting RNAs (piRNAs) have long been associated with the silencing of transposable elements (TEs). However, over 20,000 unique species of piRNAs mapped to the human genome are more than the relatively few presumably required to regulate the known human transposon classes. Here, we present the results of the first genome-wide effort to study the effects of piRNAs on gene specific DNA methylation. We found that exon-derived piRNAs consist almost universally of species with 10 or fewer genomic copies, whereas piRNAs existing in high copies originate predominately from intronic and intergenic regions. Genome-wide methylation profiling following transfection of human somatic cells with piRNA mimics revealed methylation changes at numerous genic loci in single copy piRNA-transfected cells. Moreover, genomic regions directly adjacent to differentially methylated CpG sites were enriched for sequence matches to the transfected piRNAs. These findings suggest that a subset of single copy piRNAs may be able to induce DNA methylation at non-TE genic loci, a process that may be mediated in part by direct binding to either genomic DNA or nascent mRNA near target CpG sites.
authors.affiliation: a Yale University School of Public Health ; New Haven , CT USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Fu
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Jacobs
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D005260:Female; D015894:Genome, Human; D006801:Humans; D047468:Immunoprecipitation; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D004251:DNA Transposable Elements; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: DNA methylation; gene regulation; genomic distribution; human somatic cells; piRNA