title: Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc.
abstract: Long non-coding RNAs (lncRNAs), transcribed from the intergenic regions of animal genomes, play important roles in key biological processes. In mice, Zdbf2linc was recently identified as an lncRNA isoform of the paternally expressed imprinted Zdbf2 gene. The functional role of Zdbf2linc remains undefined, but it may control parent-of-origin-specific expression of protein-coding neighbors through epigenetic modification in cis, similar to imprinted Nespas, Kcnq1ot1 and Airn lncRNAs. Here, we identified a novel imprinted long-range non-coding RNA, termed GPR1AS, in the human GPR1-ZDBF2 intergenic region. Although GPR1AS contains no human ZDBF2 exons, this lncRNA is transcribed in the antisense orientation from the GPR1 intron to a secondary, differentially methylated region upstream of the ZDBF2 gene (ZDBF2 DMR), similar to mouse Zdbf2linc. Interestingly, GPR1AS/Zdbf2linc is exclusively expressed in human/mouse placenta with paternal-allele-specific expression and maternal-allele-specific promoter methylation (GPR1/Gpr1 DMR). The paternal-allele specific methylation of the secondary ZDBF2 DMR was established in human placentas as well as somatic lineage. Meanwhile, the ZDBF2 gene showed stochastic paternal-allele-specific expression, possibly methylation-independent, in placental tissues. Overall, we demonstrated that epigenetic regulation mechanisms in the imprinted GPR1-GPR1AS-ZDBF2 region were well-conserved between human and mouse genomes without the high sequence conservation of the intergenic lncRNAs. Our findings also suggest that lncRNAs with highly conserved epigenetic and transcriptional regulation across species arose by divergent evolution from a common ancestor, if they do not have identical exon structures.
authors.affiliation: Department of BioScience; Tokyo University of Agriculture; Tokyo, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Eikichi
authors.initials: E
authors.lastname: Yanagisawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sakashita
authors.forename: Naoko
authors.initials: N
authors.lastname: Sugawara
authors.forename: Shiori
authors.initials: S
authors.lastname: Kumakura
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Ogawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kono
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: C504821:GPR1 protein, human; D062085:RNA, Long Noncoding; D043562:Receptors, G-Protein-Coupled
keywords: DNA methylation; antisense RNA; genomic imprinting; lncRNA; placenta