Dissemin is shutting down on January 1st, 2025

Published in

Nature Research, Nature Communications, 1(7), 2016

DOI: 10.1038/ncomms12091

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Extra-coding RNAs regulate neuronal DNA methylation dynamics

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Preprint: archiving allowed
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Data provided by SHERPA/RoMEO

Abstract

AbstractEpigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states.