Extra-coding RNAs regulate neuronal DNA methylation dynamics

Epigenetic 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. DNA methylation in the brain is a dynamic process, but gene-specific regulation of this process is poorly understood. Here, Day and colleagues show that extra-coding RNAs interact with DNA methyltransferases and regulate neuronal DNA methylation to control gene expression in locus-specific manner in neurons.

• Publication year

  2016

• Venue

  Nature Communications

• Publication date

  2016-07-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms12091PMID 27384705PMCID 4941050
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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