ArticleAddiction biology2021
Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways.
Article in Addiction biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.Molecular psychiatry · 2025Pooled it
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Modifications on histone tails in psychiatric disorders.EC psychology and psychiatry · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- Dysregulation of Central-Medial Amygdala Histone Modifiers in Preclinical Models of Ethanol Exposure.Addiction biology · 2025Review
- Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life.Alcohol, clinical & experimental research · 2025Article
- A Novel Role for the Histone Demethylase JMJD3 in Mediating Heroin-Induced Relapse-Like Behaviors.Biological psychiatry · 2025Article
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- Epigenetic Dysregulation in Alcohol-Associated Behaviors: Preclinical and Clinical Evidence.Current topics in behavioral neurosciences · 2025Review
- Chronic ethanol exposure decreases H3K27me3 in the Il6 promoter region of macrophages and generates persistent dysfunction on neutrophils during fungal infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.Journal of pharmaceutical analysis · 2024Review
- Epigenetic heterogeneity shapes the transcriptional landscape of regional microglia.bioRxiv : the preprint server for biology · 2024Article
- Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System.International journal of molecular sciences · 2024Article
- PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization.Genome biology · 2024Article
- Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex.Frontiers in pharmacology · 2024Article
- Upregulation of lysine-specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation-dependent production of TNF-α in the dorsal root ganglia and spinal dorsal horn in rats.CNS neuroscience & therapeutics · 2023Article
- Transcriptional and epigenetic regulation of microglia in substance use disorders.Molecular and cellular neurosciences · 2023Review
- Alcohol-Associated Tissue Injury: Current Views on Pathophysiological Mechanisms.Annual review of physiology · 2022Review
- Current and Future Perspectives of Noncoding RNAs in Brain Function and Neuropsychiatric Disease.Biological psychiatry · 2022Review
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Epigenetic enzymes oversee long-term changes in gene expression by integrating genetic and environmental cues. While there are hundreds of enzymes that control histone and DNA modifications, their potential roles in substance abuse and alcohol dependence remain underexplored. A few recent studies have suggested that epigenetic processes could underlie transcriptomic and behavioral hallmarks of alcohol addiction. In the present study, we sought to identify epigenetic enzymes in the brain that are dysregulated during protracted abstinence as a consequence of chronic and intermittent alcohol exposure. Through quantitative mRNA expression analysis of over 100 epigenetic enzymes, we identified 11 that are significantly altered in alcohol-dependent rats compared with controls. Follow-up studies of one of these enzymes, the histone demethylase KDM6B, showed that this enzyme exhibits region-specific dysregulation in the prefrontal cortex and nucleus accumbens of alcohol-dependent rats. KDM6B was also upregulated in the human alcoholic brain. Upregulation of KDM6B protein in alcohol-dependent rats was accompanied by a decrease of trimethylation levels at histone H3, lysine 27 (H3K27me3), consistent with the known demethylase specificity of KDM6B. Subsequent epigenetic (chromatin immunoprecipitation [ChIP]-sequencing) analysis showed that alcohol-induced changes in H3K27me3 were significantly enriched at genes in the IL-6 signaling pathway, consistent with the well-characterized role of KDM6B in modulation of inflammatory responses. Knockdown of KDM6B in cultured microglial cells diminished IL-6 induction in response to an inflammatory stimulus. Our findings implicate a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory signaling pathways that are known to underlie the development of alcohol addiction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.