ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 158 citations in OpenAlex.
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.Molecular cell · 2026Article
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.bioRxiv : the preprint server for biology · 2026Article
- Wiedemann-Steiner Syndrome (WSS): A Neonatal Case Report Expanding the Phenotypic Spectrum of a Previously Reported Missense Variant.International journal of molecular sciences · 2026Review
- KAT6A is essential for developmental control gene expression in neural stem and progenitor cells.PLoS genetics · 2026Article
- SA supplementation during lactation promotes learning and memory by reducing H3K27me3 levels.Journal of advanced research · 2026Article
- Absence of Ledgf in mouse brain affects the Kmt2a/b and polycomb balance, synaptic transmission and motor function.Acta neuropathologica communications · 2026Article
- Review
- KMT2A-Mediated transcriptional regulation in stemness and cancer: molecular mechanisms and therapeutic opportunities.Medical oncology (Northwood, London, England) · 2025Review
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.Cell reports · 2025Article
- Behavioural impairments in a mouse model of Kabuki syndrome associated with dopaminergic and neuroinflammatory modulations.Acta neuropsychiatrica · 2025Article
- Gene Expression Profiling in the Cortex of Fabp4 Knockout Mice.Neuropsychopharmacology reports · 2025Article
- MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation.Science advances · 2024Article
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Article
- Histone 3 Trimethylation Patterns are Associated with Resilience or Stress Susceptibility in a Rat Model of Major Depression Disorder.Molecular neurobiology · 2024Article
- Menin Deficiency Induces Autism-Like Behaviors by Regulating Foxg1 Transcription and Participates in Foxg1-Related Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Haplotype-resolved and chromosome-scale genomes provide insights into co-adaptation between the Amur tiger and Amur leopard.Zoological research · 2024Article
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other cis-regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase, Kmt2a/Mixed-lineage leukemia 1 (Mll1), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the Mll1 ortholog Kmt2b/Mll2 in PFC. Impaired working memory after Kmt2a/Mll1 ablation in PFC neurons was associated with loss of training-induced transient waves of Arc immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in Mll1-deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at <50 loci, including the homeodomain transcription factor Meis2. Small RNA-mediated Meis2 knockdown in PFC was associated with working memory defects similar to those elicited by Mll1 deletion. Therefore, mature prefrontal neurons critically depend on maintenance of Mll1-regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion.
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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.