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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.

SUBMITTER: Tomikawa J

PROVIDER: S-EPMC3186369 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines.

Tomikawa Junko J Shimokawa Hiroko H Uesaka Masahiro M Yamamoto Naoki N Mori Yuji Y Tsukamura Hiroko H Maeda Kei-ichiro K Imamura Takuya T

The Journal of biological chemistry 20110815 40

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 ra ...[more]

PMID: 21844201

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Project description:BackgroundThere are over 100 published studies of a therapy called Emotional Freedom Techniques (EFT). This popular form of energy psychology combines elements of established methods like cognitive therapy with acupressure. Our group reported the first evidence of its mechanisms of action at the molecular level, showing that it can influence levels of the stress hormone cortisol.ObjectivesGiven recent advances in molecular genomics that have identified noncoding ribonucleic acid (RNA) molecules as important regulators of gene expression, the aim of this study is to explore the possibility that microRNAs play a role in mediating the effects of EFT.MethodsWe measured microRNA levels in stored blood samples from our previous study in which veterans were randomized into an EFT group receiving EFT and treatment as usual throughout a 10-week intervention period, and a control group receiving only treatment as usual during the intervention period and then receiving EFT. A broad panel of 800 microRNAs was probed using a multiplexed, direct hybridization, and detection system.ResultsAll of the microRNA targets were expressed at low levels and most were below thresholds established by negative control probes. Baseline variability was determined using samples collected from the control group at the start and end of the intervention period, and used to filter out targets that were too noisy under control conditions to be able to distinguish a response to treatment. Analysis of the remaining viable targets found a general trend of reduced expression following EFT, compared to expression levels in samples from the control group during the intervention period. The most notable decreases in expression levels were found for 2 microRNAs: let-7b and let-7c, although no significance was found after adjusting for multiple comparisons.ConclusionsThese preliminary data support the feasibility of measuring microRNA expression level changes that correlate with effective EFT therapy.

Dataset Information

Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines.

Publications

Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines.

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