ArticleMolecular psychiatry2022
KDM6B cooperates with Tau and regulates synaptic plasticity and cognition via inducing VGLUT1/2.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.Communications biology · 2026Article
- SA supplementation during lactation promotes learning and memory by reducing H3K27me3 levels.Journal of advanced research · 2026Article
- AIF3 splicing variant elicits mitochondrial malfunction via the concurrent dysregulation of electron transport chain and glutathione-redox homeostasis.Nature communications · 2025Article
- Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls.Frontiers in aging neuroscience · 2025Article
- Impact of KDM6B mosaic brain knockout on synaptic function and behavior.Scientific reports · 2024Article
- Identification of a molecular network regulated by multiple ASD high risk genes.Human molecular genetics · 2024Article
- Article
- Association of reduced cerebrospinal fluid NPTX2 levels with postoperative delirium in patients undergoing knee/hip replacement: a prospective cohort study.Aging clinical and experimental research · 2024Article
- Deep Trans-Omic Network Fusion for Molecular Mechanism of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Desipramine reverses remote memory deficits by activating calmodulin-CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome.General psychiatry · 2024Article
- Tau mediates the reshaping of the transcriptional landscape toward intermediate Alzheimer's disease stages.Frontiers in cell and developmental biology · 2024Article
- Simulated vestibular spatial disorientation mouse model under coupled rotation revealing potential involvement of Slc17a6.iScience · 2023Article
- Tonic activin signaling shapes cellular and synaptic properties of CA1 neurons mainly in dorsal hippocampus.iScience · 2023Article
- The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder.American journal of human genetics · 2023Article
- Can accelerated ageing models inform us on age-related tauopathies?Aging cell · 2023Review
- Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis.Frontiers in immunology · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The excitatory neurotransmitter glutamate shapes learning and memory, but the underlying epigenetic mechanism of glutamate regulation in neuron remains poorly understood. Here, we showed that lysine demethylase KDM6B was expressed in excitatory neurons and declined in hippocampus with age. Conditional knockout of KDM6B in excitatory neurons reduced spine density, synaptic vesicle number and synaptic activity, and impaired learning and memory without obvious effect on brain morphology in mice. Mechanistically, KDM6B upregulated vesicular glutamate transporter 1 and 2 (VGLUT1/2) in neurons through demethylating H3K27me3 at their promoters. Tau interacted and recruited KDM6B to the promoters of Slc17a7 and Slc17a6, leading to a decrease in local H3K27me3 levels and induction of VGLUT1/2 expression in neurons, which could be prevented by loss of Tau. Ectopic expression of KDM6B, VGLUT1, or VGLUT2 restored spine density and synaptic activity in KDM6B-deficient cortical neurons. Collectively, these findings unravel a fundamental mechanism underlying epigenetic regulation of synaptic plasticity and cognition.
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