title: Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines.
abstract: A growing number of noncoding RNAs (ncRNAs) are thought to be involved in sequence-specific alterations of epigenetic processes, mostly causing gene repression. In this study, promoter-associated ncRNAs (pancRNAs >200 nucleotides in size) that were endogenously generated from the sense strand at Map2b, antisense strand at Nefl, and both strands at Vim were investigated regarding their epigenetic potential as positive or negative regulators in rat pheochromocytoma (PC12) and fibroblast (normal rat kidney) cell lines. The respective antisense pancRNAs were associated with several active chromatin marks at the Nefl and Vim promoters. Forced expression of fragments expressing the antisense pancRNAs caused sequence-specific DNA demethylation, whereas a decrease of expression induced methylation of the same sequences. In contrast, perturbing the expression of the two sense pancRNAs did not change the DNA methylation status. These results suggest that a fraction of naturally occurring ncRNAs acts in cis as a single-stranded form and that the transcriptional orientation of pancRNA is important for the establishment of sequence-specific epigenetic modifications consistent with open chromatin structure.
authors.affiliation: Division of Behavioral Biology, National Institute for Basic Biology, Nishigonaka 38, Okazaki 444-8585, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Tomikawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Uesaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mori
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Maeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Imamura
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D008297:Male; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry*; D016372:RNA, Antisense / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002843:Chromatin; D016372:RNA, Antisense; D022661:RNA, Untranslated; D012313:RNA