Cargando…
Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534961/ https://www.ncbi.nlm.nih.gov/pubmed/28485726 http://dx.doi.org/10.1038/tp.2017.93 |
_version_ | 1783253813237383168 |
---|---|
author | Gross, J A Pacis, A Chen, G G Drupals, M Lutz, P-E Barreiro, L B Turecki, G |
author_facet | Gross, J A Pacis, A Chen, G G Drupals, M Lutz, P-E Barreiro, L B Turecki, G |
author_sort | Gross, J A |
collection | PubMed |
description | 5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field. |
format | Online Article Text |
id | pubmed-5534961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55349612017-08-01 Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals Gross, J A Pacis, A Chen, G G Drupals, M Lutz, P-E Barreiro, L B Turecki, G Transl Psychiatry Original Article 5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field. Nature Publishing Group 2017-05 2017-05-09 /pmc/articles/PMC5534961/ /pubmed/28485726 http://dx.doi.org/10.1038/tp.2017.93 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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-nc-sa/4.0/ |
spellingShingle | Original Article Gross, J A Pacis, A Chen, G G Drupals, M Lutz, P-E Barreiro, L B Turecki, G Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title | Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title_full | Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title_fullStr | Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title_full_unstemmed | Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title_short | Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
title_sort | gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534961/ https://www.ncbi.nlm.nih.gov/pubmed/28485726 http://dx.doi.org/10.1038/tp.2017.93 |
work_keys_str_mv | AT grossja genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT pacisa genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT chengg genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT drupalsm genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT lutzpe genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT barreirolb genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals AT tureckig genebody5hydroxymethylationisassociatedwithgeneexpressionchangesintheprefrontalcortexofdepressedindividuals |