ArticleJCI insight2019
Precocious neuronal differentiation and disrupted oxygen responses in Kabuki syndrome.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Clinical, cellular, and genomic consequences of a population-enrichedResearch square · 2026Article
- Joint profiling of cell morphology and gene expression during in vitro neurodevelopment.eLife · 2025Article
- KMT2D temporally activates neuronal transcriptional factor genes to mediate cerebellar granule cell differentiation.Science advances · 2025Article
- Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons.PLoS genetics · 2025Article
- Higher order interaction analysis quantifies coordination in the epigenome revealing novel biological relationships in Kabuki syndrome.Briefings in bioinformatics · 2024Article
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.Genome research · 2024Article
- The omics era: a nexus of untapped potential for Mendelian chromatinopathies.Human genetics · 2024Review
- KMT2D regulates activation, localization, and integrin expression by T-cells.Frontiers in immunology · 2024Article
- Clinical and molecular characteristics of Kabuki syndrome patients with missense variants-novel features and literature review.Frontiers in genetics · 2024Article
- SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder.Birth defects research · 2023Review
- Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1.Birth defects research · 2023Review
- Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.bioRxiv : the preprint server for biology · 2023Article
- KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Somatic mutations alter the differentiation outcomes of iPSC-derived neurons.Cell genomics · 2023Article
- The role of histone methyltransferases in neurocognitive disorders associated with brain size abnormalities.Frontiers in neuroscience · 2023Review
- Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).Human molecular genetics · 2022Article
- Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Universal prediction of cell-cycle position using transfer learning.Genome biology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Chromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability disorder Kabuki syndrome 1 (KS1). Critical roles for KMT2D are established in various non-neural tissues, but the effects of KMT2D loss in brain cell development have not been described. We conducted parallel studies of proliferation, differentiation, transcription, and chromatin profiling in KMT2D-deficient human and mouse models to define KMT2D-regulated functions in neurodevelopmental contexts, including adult-born hippocampal NSPCs in vivo and in vitro. We report cell-autonomous defects in proliferation, cell cycle, and survival, accompanied by early NSPC maturation in several KMT2D-deficient model systems. Transcriptional suppression in KMT2D-deficient cells indicated strong perturbation of hypoxia-responsive metabolism pathways. Functional experiments confirmed abnormalities of cellular hypoxia responses in KMT2D-deficient neural cells and accelerated NSPC maturation in vivo. Together, our findings support a model in which loss of KMT2D function suppresses expression of oxygen-responsive gene programs important to neural progenitor maintenance, resulting in precocious neuronal differentiation in a mouse model of KS1.
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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.