Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol

Zhifeng Zhou, Qiaoping Yuan, Deborah C Mash, David Goldman

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using wholegenome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine-and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.

Original languageEnglish
Pages (from-to)6626-6631
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number16
DOIs
StatePublished - Apr 19 2011

Fingerprint

Cocaine
Epigenomics
Hippocampus
Alcohols
Histones
Gene Expression
Histone Code
Long-Term Memory
Oxidative Phosphorylation
Mitochondrial Membranes
Regulator Genes
Immunoprecipitation
Neurodegenerative Diseases
Pharmaceutical Preparations
Energy Metabolism
Lysine
Learning
RNA
Messenger RNA
DNA

Keywords

  • Drug addiction
  • Histone methylation

ASJC Scopus subject areas

  • General

Cite this

Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol. / Zhou, Zhifeng; Yuan, Qiaoping; Mash, Deborah C; Goldman, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 16, 19.04.2011, p. 6626-6631.

Research output: Contribution to journalArticle

@article{312f4525145e49478300c5af4606856b,
title = "Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol",
abstract = "The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using wholegenome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine-and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.",
keywords = "Drug addiction, Histone methylation",
author = "Zhifeng Zhou and Qiaoping Yuan and Mash, {Deborah C} and David Goldman",
year = "2011",
month = "4",
day = "19",
doi = "10.1073/pnas.1018514108",
language = "English",
volume = "108",
pages = "6626--6631",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "16",

}

TY - JOUR

T1 - Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol

AU - Zhou, Zhifeng

AU - Yuan, Qiaoping

AU - Mash, Deborah C

AU - Goldman, David

PY - 2011/4/19

Y1 - 2011/4/19

N2 - The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using wholegenome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine-and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.

AB - The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using wholegenome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine-and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.

KW - Drug addiction

KW - Histone methylation

UR - http://www.scopus.com/inward/record.url?scp=79955583858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955583858&partnerID=8YFLogxK

U2 - 10.1073/pnas.1018514108

DO - 10.1073/pnas.1018514108

M3 - Article

VL - 108

SP - 6626

EP - 6631

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 16

ER -