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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 presentl...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941050/ https://www.ncbi.nlm.nih.gov/pubmed/27384705 http://dx.doi.org/10.1038/ncomms12091 |
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author | Savell, Katherine E. Gallus, Nancy V. N. Simon, Rhiana C. Brown, Jordan A. Revanna, Jasmin S. Osborn, Mary Katherine Song, Esther Y. O'Malley, John J. Stackhouse, Christian T. Norvil, Allison Gowher, Humaira Sweatt, J. David Day, Jeremy J. |
author_facet | Savell, Katherine E. Gallus, Nancy V. N. Simon, Rhiana C. Brown, Jordan A. Revanna, Jasmin S. Osborn, Mary Katherine Song, Esther Y. O'Malley, John J. Stackhouse, Christian T. Norvil, Allison Gowher, Humaira Sweatt, J. David Day, Jeremy J. |
author_sort | Savell, Katherine E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4941050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49410502016-09-06 Extra-coding RNAs regulate neuronal DNA methylation dynamics Savell, Katherine E. Gallus, Nancy V. N. Simon, Rhiana C. Brown, Jordan A. Revanna, Jasmin S. Osborn, Mary Katherine Song, Esther Y. O'Malley, John J. Stackhouse, Christian T. Norvil, Allison Gowher, Humaira Sweatt, J. David Day, Jeremy J. Nat Commun Article 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. Nature Publishing Group 2016-07-07 /pmc/articles/PMC4941050/ /pubmed/27384705 http://dx.doi.org/10.1038/ncomms12091 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Savell, Katherine E. Gallus, Nancy V. N. Simon, Rhiana C. Brown, Jordan A. Revanna, Jasmin S. Osborn, Mary Katherine Song, Esther Y. O'Malley, John J. Stackhouse, Christian T. Norvil, Allison Gowher, Humaira Sweatt, J. David Day, Jeremy J. Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title | Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title_full | Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title_fullStr | Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title_full_unstemmed | Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title_short | Extra-coding RNAs regulate neuronal DNA methylation dynamics |
title_sort | extra-coding rnas regulate neuronal dna methylation dynamics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941050/ https://www.ncbi.nlm.nih.gov/pubmed/27384705 http://dx.doi.org/10.1038/ncomms12091 |
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