ArticleSchizophrenia research2013
Histone methylation at H3K9: evidence for a restrictive epigenome in schizophrenia.
Article in Schizophrenia research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings.Molecular psychiatry · 2020Pooled it
- Trial
- Histone Modifications in Psychiatry: From Canonical Marks to Neurotransmitter-Mediated Epigenetic Signatures.Alpha psychiatry · 2026Review
- The dual G9a inhibitor and histamine H3 receptor antagonist A-366 improves repetitive and social behaviors and attenuates neuroinflammation in BTBR T + tf/J mice.Scientific reports · 2026Article
- Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions.Current pharmaceutical design · 2026Review
- Modifications on histone tails in psychiatric disorders.EC psychology and psychiatry · 2026Article
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Epigenetic Control in Schizophrenia.Sub-cellular biochemistry · 2025Review
- Targeting the Tumor Epigenetic Regulator SETDB1 for Tumor Therapy.Current cancer drug targets · 2025Review
- Opposite and Differently Altered Postmortem Changes in H3 and H3K9me3 Patterns in the Rat Frontal Cortex and Hippocampus.Epigenomes · 2024Article
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Epigenetic Targets in Schizophrenia Development and Therapy.Brain sciences · 2023Review
- Methylome-wide Association Study of Patients with Recent-onset Psychosis.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022Article
- The role of histone modifications: from neurodevelopment to neurodiseases.Signal transduction and targeted therapy · 2022Review
- Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia.Nature communications · 2022Article
- HP1 maintains protein stability of H3K9 methyltransferases and demethylases.EMBO reports · 2022Article
- Histone Acetylation and Methylation Underlie Oligodendroglial and Myelin Susceptibility in Schizophrenia.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveEpigenetic changes are stable and long-lasting chromatin modifications that regulate genomewide and local gene activity. The addition of two methyl groups to the 9th lysine of histone 3 (H3K9me2) by histone methyltransferases (HMT) leads to a restrictive chromatin state, and thus reduced levels of gene transcription. Given the numerous reports of transcriptional down-regulation of candidate genes in schizophrenia, we tested the hypothesis that this illness can be characterized by a restrictive epigenome.
methodsWe obtained parietal cortical samples from the Stanley Foundation Neuropathology Consortium and lymphocyte samples from the University of Illinois at Chicago (UIC). In both tissues we measured mRNA expression of HMTs GLP, SETDB1 and G9a via real-time RT-PCR and H3K9me2 levels via western blot. Clinical rating scales were obtained from the UIC cohort.
resultsA diagnosis of schizophrenia is a significant predictor for increased GLP, SETDB1 mRNA expression and H3K9me2 levels in both postmortem brain and lymphocyte samples. G9a mRNA is significantly increased in the UIC lymphocyte samples as well. Increased HMT mRNA expression is associated with worsening of specific symptoms, longer durations of illness and a family history of schizophrenia.
conclusionsThese data support the hypothesis of a restrictive epigenome in schizophrenia, and may associate with symptoms that are notoriously treatment resistant. The histone methyltransferases measured here are potential future therapeutic targets for small molecule pharmacology, and better patient prognosis.
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Registered trials
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