ArticleMolecular psychiatry2021
Cocaine-related DNA methylation in caudate neurons alters 3D chromatin structure of the IRXA gene cluster.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Why animal models are still needed for discoveries in mental health research.Journal of psychiatry & neuroscience : JPN · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Decoding Encoded Cravings: Epigenetic Drivers of Addiction.Brain sciences · 2025Review
- Review
- Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder.Translational psychiatry · 2024Article
- Review
- Substance-Induced Psychiatric Disorders, Epigenetic and Microbiome Alterations, and Potential for Therapeutic Interventions.Brain sciences · 2024Review
- Incubation of methamphetamine craving in punishment-resistant individuals is associated with activation of specific gene networks in the rat dorsal striatum.Molecular psychiatry · 2024Article
- Epigenome-wide association study on methamphetamine dependence.Addiction biology · 2024Article
- Low Dopamine D2 Receptor Expression Drives Gene Networks Related to GABA, cAMP, Growth and Neuroinflammation in Striatal Indirect Pathway Neurons.Biological psychiatry global open science · 2023Article
- Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits.BMC genomics · 2023Article
- 3D genome alterations and editing in pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- DNA methylation in cocaine use disorder-An epigenome-wide approach in the human prefrontal cortex.Frontiers in psychiatry · 2023Article
- Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the nucleus accumbens in mice.Psychopharmacology · 2022Article
- Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats.Molecular neurobiology · 2022Article
- Article
- DNA Epigenetics in Addiction Susceptibility.Frontiers in genetics · 2022Review
- Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum.iScience · 2021Article
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of cocaine dependence in human post-mortem caudate tissue. We focused on the Iroquois Homeobox A (IRXA) gene cluster, where hypomethylation in exon 3 of IRX2 in neuronal nuclei was associated with cocaine dependence. We replicated this finding in an independent cohort and found similar results in the dorsal striatum from cocaine self-administering mice. Using epigenome editing and 3C assays, we demonstrated a causal relationship between methylation within the IRX2 gene body, CTCF protein binding, three-dimensional (3D) chromatin interaction, and gene expression. Together, these findings suggest that cocaine-related hypomethylation of IRX2 contributes to the development and maintenance of cocaine dependence through alterations in 3D chromatin structure in the caudate nucleus.
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