Next Article in Journal
HiSeeker: Detecting High-Order SNP Interactions Based on Pairwise SNP Combinations
Previous Article in Journal
MYC Deregulation in Primary Human Cancers
Previous Article in Special Issue
Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Genes 2017, 8(6), 152; doi:10.3390/genes8060152

DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age

1
James J. Peters VA Medical Center, Bronx, NY 10468, USA
2
The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
3
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD 21205, USA
4
Department of Biostatistics and Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
5
Center for Computational Biology, Johns Hopkins University, Baltimore, MD, 21205, USA
6
Hospital for Special Surgery, New York, NY 10021, USA
7
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
8
Department of Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dennis R. Grayson
Received: 14 February 2017 / Revised: 21 April 2017 / Accepted: 25 May 2017 / Published: 30 May 2017
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
View Full-Text   |   Download PDF [695 KB, uploaded 30 May 2017]   |  

Abstract

We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0.001). DMSs and corresponding genes (DMGs) in heroin users showed significant differences in the preferential context of hyper and hypo DM. HyperDMSs were enriched in gene bodies and exons but depleted in promoters, whereas hypoDMSs were enriched in promoters and enhancers. In addition, hyperDMGs showed preference for genes expressed specifically by glutamatergic as opposed to GABAergic neurons and enrichment for axonogenesis- and synaptic-related gene ontology categories, whereas hypoDMGs were enriched for transcription factor activity- and gene expression regulation-related terms. Finally, we found that the DNAm-based “epigenetic age” of neurons from heroin users was younger than that in controls. Suicide-related results were more difficult to interpret. Collectively, these findings suggest that the observed DNAm differences could represent functionally significant marks of heroin-associated plasticity in the OFC. View Full-Text
Keywords: DNA methylation; drug addiction; heroin; suicide; brain; neurons; human DNA methylation; drug addiction; heroin; suicide; brain; neurons; human
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kozlenkov, A.; Jaffe, A.E.; Timashpolsky, A.; Apontes, P.; Rudchenko, S.; Barbu, M.; Byne, W.; Hurd, Y.L.; Horvath, S.; Dracheva, S. DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age. Genes 2017, 8, 152.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top