TY - JOUR
T1 - Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines
AU - Tomikawa, Junko
AU - Shimokawa, Hiroko
AU - Uesaka, Masahiro
AU - Yamamoto, Naoki
AU - Mori, Yuji
AU - Tsukamura, Hiroko
AU - Maeda, Kei Ichiro
AU - Imamura, Takuya
PY - 2011/10/7
Y1 - 2011/10/7
N2 - Agrowing number of noncoding RNAs (ncRNAs) are thought to be involved in sequence-specific alterations of epigenetic processes, mostly causing gene repression. In this study, promoterassociated 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.
AB - Agrowing number of noncoding RNAs (ncRNAs) are thought to be involved in sequence-specific alterations of epigenetic processes, mostly causing gene repression. In this study, promoterassociated 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.
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U2 - 10.1074/jbc.M111.275750
DO - 10.1074/jbc.M111.275750
M3 - Article
C2 - 21844201
AN - SCOPUS:80053428353
SN - 0021-9258
VL - 286
SP - 34788
EP - 34799
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -