ArticleNature communications2021
Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 60 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
- Sh3rf3 Deficiency drives autism-like behaviors via presynaptic dysfunction in mice.Molecular psychiatry · 2026Article
- Voluntary wheel running exercise attenuates VPA-induced ASD-like behaviors in male rats: implication of the vagal pathway of the gut-brain axis.NPJ biofilms and microbiomes · 2026Article
- Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence.Biomolecules · 2026Article
- Reducing methylation of histone 3.3 lysine 4 in the medial ganglionic eminence and hypothalamus recapitulates neurodevelopmental disorder phenotypes.Nature communications · 2026Article
- Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease.Molecular psychiatry · 2026Article
- Synaptic mechanisms for differential severity of social preference deficits in male and female mice induced by diminished activity-dependent BDNF.Frontiers in neuroscience · 2026Article
- Targeting Ash1L-STING Axis Restores NK Cell Function and Ameliorates Immune-Mediated Bone Marrow Failure Diseases.International journal of biological sciences · 2026Article
- A rat Satb1 truncation causes neurodevelopmental abnormalities recapitulating the symptoms of patients with SATB1 mutations.Acta pharmacologica Sinica · 2025Article
- Article
- 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
- Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.Nature communications · 2025Article
- CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model.Neurobiology of disease · 2025Article
- Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis.Cell reports. Medicine · 2025Article
- Novel heterozygousFrontiers in neurology · 2025Article
- Article
- ASH1L in Hepatoma Cells and Hepatic Stellate Cells Promotes Fibrosis-Associated Hepatocellular Carcinoma by Modulating Tumor-Associated Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinical and Genetic Characterization of Adolescent-Onset Epilepsy: A Single-Center Experience in Republic of Korea.Biomedicines · 2024Article
- Identification of a molecular network regulated by multiple ASD high risk genes.Human molecular genetics · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
ASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.
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