ArticleMolecular psychiatry2020
Amelioration of autism-like social deficits by targeting histone methyltransferases EHMT1/2 in Shank3-deficient mice.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 78 citations in OpenAlex.
- Cognitive and synaptic impairment induced by deficiency of autism risk gene Smarcc2 and its rescue by histone deacetylase inhibition.Molecular psychiatry · 2026Article
- Epigenetic treatment of synaptic and behavioral deficits in Dyrk1a-mutant mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- 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
- Domain-specific and sex-dependent behavioral alterations in the BTBR mouse model of autism.Frontiers in behavioral neuroscience · 2026Article
- Liquid-liquid phase separation couples MKRN2-mediated ubiquitination of CSDE1 with neurodevelopmental disorders.Frontiers in cellular neuroscience · 2026Article
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition.Autism research : official journal of the International Society for Autism Research · 2025Article
- Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Clinical characteristics and genetic analysis of four pediatric patients with Kleefstra syndrome.BMC medical genomics · 2024Article
- The Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.Cells · 2024Review
- Animal Models of Autistic-like Behavior in Rodents: A Scoping Review and Call for a Comprehensive Scoring System.International journal of molecular sciences · 2024Article
- Targeting epigenetic enzymes for autism treatment.Trends in pharmacological sciences · 2024Review
- Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.Cellular and molecular life sciences : CMLS · 2024Article
- An epigenetic mechanism of social isolation stress in adolescent female mice.Neurobiology of stress · 2024Article
- Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs.Molecular autism · 2024Article
- YBX1-Mediated DNA Methylation-Dependent SHANK3 Expression in PBMCs and Developing Cortical Interneurons in Schizophrenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.The international journal of neuropsychopharmacology · 2023Article
- Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits.Translational psychiatry · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Many of the genes disrupted in autism are identified as histone-modifying enzymes and chromatin remodelers, most prominently those that mediate histone methylation/demethylation. However, the role of histone methylation enzymes in the pathophysiology and treatment of autism remains unknown. To address this, we used mouse models of haploinsufficiency of the Shank3 gene (a highly penetrant monogenic autism risk factor), which exhibits prominent autism-like social deficits. We found that histone methyltransferases EHMT1 and EHMT2, as well as histone lysine 9 dimethylation (specifically catalyzed by EHMT1/2), were selectively increased in the prefrontal cortex (PFC) of Shank3-deficient mice and autistic human postmortem brains. Treatment with the EHMT1/2 inhibitor UNC0642 or knockdown of EHMT1/2 in PFC induced a robust rescue of autism-like social deficits in Shank3-deficient mice, and restored NMDAR-mediated synaptic function. Activity-regulated cytoskeleton-associated protein (Arc) was identified as one of the causal factors underlying the rescuing effects of UNC0642 on NMDAR function and social behaviors in Shank3-deficient mice. UNC0642 treatment also restored a large set of genes involved in neural signaling in PFC of Shank3-deficient mice. These results suggest that targeting histone methylation enzymes to adjust gene expression and ameliorate synaptic defects could be a potential therapeutic strategy for autism.
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