ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Neuronal Deletion of Kmt2a/Mll1 Histone Methyltransferase in Ventral Striatum is Associated with Defective Spike-Timing-Dependent Striatal Synaptic Plasticity, Altered Response to Dopaminergic Drugs, and Increased Anxiety.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
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- KMT2A-Mediated transcriptional regulation in stemness and cancer: molecular mechanisms and therapeutic opportunities.Medical oncology (Northwood, London, England) · 2025Review
- Molecular Basis of Anxiety: A Comprehensive Review of 2014-2024 Clinical and Preclinical Studies.International journal of molecular sciences · 2025Review
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- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
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- Zhi-zi-chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter.Journal of cellular and molecular medicine · 2024Article
- Genetic influences on motor learning and performance and superperforming mutants revealed by random mutational survey of the mouse genome.The Journal of physiology · 2024Article
- Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.Current neuropharmacology · 2024Article
- Structural variation of the coding and non-coding human pharmacogenome.NPJ genomic medicine · 2023Article
- Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in Major Depressive Disorder.Molecular neurobiology · 2023Article
- Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing.Journal of the International Neuropsychological Society : JINS · 2023Article
- Critical periods and Autism Spectrum Disorders, a role for sleep.Neurobiology of sleep and circadian rhythms · 2023Article
- RNA methyltransferase NSun2 deficiency promotes neurodegeneration through epitranscriptomic regulation of tau phosphorylation.Acta neuropathologica · 2023Article
- Review
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Lysine (K) methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4 methylation, a histone modification enriched at promoters and enhancers, are widely expressed throughout the brain, but molecular and cellular phenotypes in subcortical areas remain poorly explored. We report that Kmt2a conditional deletion in postnatal forebrain is associated with excessive nocturnal activity and with absent or blunted responses to stimulant and dopaminergic agonist drugs, in conjunction with near-complete loss of spike-timing-dependent long-term potentiation in medium spiny neurons (MSNs). Selective ablation of Kmt2a, but not the ortholog Kmt2b, in adult ventral striatum/nucleus accumbens neurons markedly increased anxiety scores in multiple behavioral paradigms. Striatal transcriptome sequencing in adult mutants identified 262 Kmt2a-sensitive genes, mostly downregulated in Kmt2a-deficient mice. Transcriptional repression includes the 5-Htr2a serotonin receptor, strongly associated with anxiety- and depression-related disorders in human and animal models. Consistent with the role of Kmt2a in promoting gene expression, the transcriptional regulators Bahcc1, Isl1, and Sp9 were downregulated and affected by H3K4 promoter hypomethylation. Therefore, Kmt2a regulates synaptic plasticity in striatal neurons and provides an epigenetic drug target for anxiety and dopamine-mediated behaviors.
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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.