Title |
The Histone H3K27 Demethylase UTX Regulates Synaptic Plasticity and Cognitive Behaviors in Mice
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Published in |
Frontiers in Molecular Neuroscience, August 2017
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DOI | 10.3389/fnmol.2017.00267 |
Pubmed ID | |
Authors |
Gang-Bin Tang, Yu-Qiang Zeng, Pei-Pei Liu, Ting-Wei Mi, Shuang-Feng Zhang, Shang-Kun Dai, Qing-Yuan Tang, Lin Yang, Ya-Jie Xu, Hai-Liang Yan, Hong-Zhen Du, Zhao-Qian Teng, Feng-Quan Zhou, Chang-Mei Liu |
Abstract |
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 Utx 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 Utx results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of Utx 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 Utx regulates a subset of genes that are involved in the regulation of dendritic morphology, synaptic transmission, and cognition. Specifically, Utx deletion disrupts expression of neurotransmitter 5-hydroxytryptamine receptor 5B (Htr5b). Restoration of Htr5b expression in newborn hippocampal neurons rescues the defects of neuronal morphology by Utx ablation. Therefore, we provide evidence that Utx plays a critical role in modulating synaptic transmission and cognitive behaviors. Utx cKO mouse models like ours provide a valuable means to study the underlying mechanisms of the etiology of Kabuki syndrome. |
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Switzerland | 1 | 100% |
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Mendeley readers
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Demographic breakdown
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Student > Ph. D. Student | 12 | 29% |
Student > Master | 5 | 12% |
Student > Bachelor | 3 | 7% |
Researcher | 3 | 7% |
Student > Postgraduate | 2 | 5% |
Other | 5 | 12% |
Unknown | 11 | 27% |
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Psychology | 1 | 2% |
Other | 3 | 7% |
Unknown | 11 | 27% |