| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Frontiers in Molecular Neuroscience, Vol 10 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5099 |
| DOI: |
10.3389/fnmol.2017.00267 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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