Kathryn Vaillancourt

Douglas Mental Health University Institute

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Gustavo Turecki

Douglas Mental Health University Institute

Carl Ernst

McGill University

Jean‐François Théroux

Group for Research in Decision Analysis

Gilles Maussion

McGill University

Naguib Mechawar

Douglas Mental Health University Institute

Alexandre Bramoullé

Douglas Mental Health University Institute

Pierre‐Eric Lutz

Institut des Neurosciences Cellulaires et Intégratives

Aurélie Masurel

McGill University and Génome Québec Innovation Centre

Geneviève Bourret

McGill University and Génome Québec Innovation Centre

Ulrike Ehlert

University of Zurich

Cooperative Institutions

McGill University

Douglas Mental Health University Institute

Jewish General Hospital

Institut Universitaire en Santé Mentale de Québec

Douglas College

McGill University Health Centre

Centre National de la Recherche Scientifique

Icahn School of Medicine at Mount Sinai

Inserm

Université de Montréal

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Molecular Psychiatry (2020)

Kathryn Vaillancourt Jennie Yang Gary G. Chen Volodymyr Yerko Jean‐François Théroux

Epigenome

10.1038/s41380-020-00909-x

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Citations (26)

Additional file 7: of Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine

Gary Chen Gross Jeffrey Lutz Pierre-Eric Kathryn Vaillancourt Gilles Maussion

5-Hydroxymethylcytosine

5-Methylcytosine

Bisulfite

Bisulfite sequencing

Terabyte

10.6084/m9.figshare.c.3668731_d7.v1

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Citations (0)

Additional file 7: of Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine

Figshare (2017)

Gary Chen Jeffrey Gross Pierre‐Eric Lutz Kathryn Vaillancourt Gilles Maussion

csv sample running sheet. (CSV 19 kb)

5-Hydroxymethylcytosine

5-Methylcytosine

Bisulfite

Bisulfite sequencing

10.6084/m9.figshare.c.3668731_d7

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Additional file 3: of Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine

Figshare (2017)

Gary Chen Jeffrey Gross Pierre‐Eric Lutz Kathryn Vaillancourt Gilles Maussion

Primers used for amplification of genomic DNA using NEXTERA XT and targeted BS-Seq (Fig. 3). (XLSX 9 kb)

5-Hydroxymethylcytosine

Bisulfite

5-Methylcytosine

Bisulfite sequencing

10.6084/m9.figshare.c.3668731_d6

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A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

Genes Brain & Behavior (2017)

Corina Nagy Kathryn Vaillancourt Gustavo Turecki

Chronic stressors, during developmental sensitive periods and beyond, contribute to the risk of developing psychiatric conditions, including major depressive disorder (MDD). Epigenetic mechanisms including DNA methylation and histone modifications, at key stress response and neurotrophin genes, are increasingly implicated in mediating this risk. Although the exact mechanisms through which stressful environmental stimuli alter the epigenome are still unclear, research from the learning and memory fields indicates that epigenomic marks can be altered, at least in part, through calcium‐dependent signaling cascades in direct response to neuronal activity. In this review, we highlight key findings from the stress, MDD, and learning and memory fields to propose a model where stress regulates downstream cellular functioning through activity‐dependent epigenetic changes. Furthermore, we suggest that both typical and novel antidepressant treatments may exert positive influence through similar, activity‐dependent pathways.

Epigenome

Epigenomics

Stressor

10.1111/gbb.12446

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Citations (44)

DNA methylation and cocaine dependence in the human striatum

Kathryn Vaillancourt

Source

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Citations (0)

DNA Methylation of a Novel Regulatory Element Within the Tyrosine Hydroxylase Gene (TH) is Dysregulated by Chronic Cocaine Dependence in the Human Striatum

SSRN Electronic Journal (2021)

Kathryn Vaillancourt Gang G. Chen Laura M. Fiori Gilles Maussion Volodymyr Yerko

Cocaine dependence is a chronic, relapsing disorder caused by lasting changes within the brain’s reward circuitry. Methylome-wide studies have identified multiple biological pathways that contain altered DNA methylation dynamics in the striatum of rodents; however, there is a lack of information about the involvement of DNA methylation in cocaine dependence in humans. Here, we generated genome-wide methylomic profiles for the nucleus accumbens, part of the ventral striatum, using human postmortem brains from a cohort of cocaine dependent and healthy controls (n=25 per group). In particular, we have identified hypermethylation of a cluster of CpGs within the gene body of tyrosine hydroxylase gene (TH), which contains a putative binding site for the early growth response 1 (EGR1) transcription factor. We replicated this finding in striatal tissue from an independent cohort (n=18 per group) and found it to be specific to striatal neuronal nuclei. Furthermore, this locus demonstrates enhancer activity in vitro, which is attenuated by methylation and enhanced by EGR1 overexpression. This is the first time that epigenetic dysregulation has been associated with cocaine dependence with respect to dopaminergic signaling and represents an important advancement in our understanding of drug neurobiology in humans.

Tyrosine 3-Monooxygenase

10.2139/ssrn.3830014

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DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects

Genes (2017)

Kathryn Vaillancourt Carl Ernst Deborah C. Mash Gustavo Turecki

Cytosine modifications, including DNA methylation, are stable epigenetic marks that may translate environmental change into transcriptional regulation. Research has begun to investigate DNA methylation dynamics in relation to cocaine use disorders. Specifically, DNA methylation machinery, including methyltransferases and binding proteins, are dysregulated in brain reward pathways after chronic cocaine exposure. In addition, numerous methylome-wide and candidate promoter studies have identified differential methylation, at the nucleotide level, in rodent models of cocaine abuse and drug seeking behavior. This review highlights the current progress in the field of cocaine-related methylation, and offers considerations for future research.

Epigenomics

10.3390/genes8050138

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Citations (39)

Molecular Convergence of Neurodevelopmental Disorders

The American Journal of Human Genetics (2014)

Elizabeth Chen Carolina Oliveira Gigek Jill A. Rosenfeld Alpha Diallo Gilles Maussion

10.1016/j.ajhg.2014.09.013

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Citations (70)

Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum

iScience (2021)

Kathryn Vaillancourt Gang G. Chen Laura M. Fiori Gilles Maussion Volodymyr Yerko

Cocaine dependence is a chronic, relapsing disorder caused by lasting changes in the brain. Animal studies have identified cocaine-related alterations in striatal DNA methylation; however, it is unclear how methylation is related to cocaine dependence in humans. We generated methylomic profiles of the nucleus accumbens using human postmortem brains from a cohort of individuals with cocaine dependence and healthy controls (n = 25 per group). We found hypermethylation in a cluster of CpGs within the gene body of tyrosine hydroxylase (TH), containing a putative binding site for the early growth response 1 (EGR1) transcription factor, which is hypermethylated in the caudate nucleus of cocaine-dependent individuals. We replicated this finding and found it to be specific to striatal neuronal nuclei. Furthermore, this locus demonstrates enhancer activity which is attenuated by methylation and enhanced by EGR1 overexpression. These results suggest that cocaine dependence alters the epigenetic regulation of dopaminergic signaling genes.

FOSB

10.1016/j.isci.2021.103169

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Citations (16)