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The Histone H3K27 Demethylase UTX Regulates Synaptic Plasticity and Cognitive Behaviors in Mice
Ist Teil von
Frontiers in molecular neuroscience, 2017-08, Vol.10, p.267-267
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Histone demethylase UTX mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish a mechanistic switch to activate large sets of genes. Mutation of
has recently been shown to be associated with Kabuki syndrome, a rare congenital anomaly syndrome with dementia. However, its biological function in the brain is largely unknown. Here, we observe that deletion of
results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of
in the hippocampus leads to reduced long-term potentiation and amplitude of miniature excitatory postsynaptic current, aberrant dendrite development and defective synapse formation. Transcriptional profiling reveals that
regulates a subset of genes that are involved in the regulation of dendritic morphology, synaptic transmission, and cognition. Specifically,
deletion disrupts expression of neurotransmitter 5-hydroxytryptamine receptor 5B (
). Restoration of
expression in newborn hippocampal neurons rescues the defects of neuronal morphology by
ablation. Therefore, we provide evidence that
plays a critical role in modulating synaptic transmission and cognitive behaviors.
cKO mouse models like ours provide a valuable means to study the underlying mechanisms of the etiology of Kabuki syndrome.