The Histone H3K27 Demethylase UTX Regulates Synaptic Plasticity and Cognitive Behaviors in Mice.
The Histone H3K27 Demethylase UTX Regulates Synaptic Plasticity and Cognitive Behaviors in Mice.
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组蛋白 H3K27 去甲基化酶 UTX 调节小鼠突触可塑性和认知行为
DOI：
10.3389/fnmol.2017.00267
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发表时间：
2017
影响因子：
4.8
通讯作者：
Liu CM
中科院分区：
文献类型：
--
作者：
Tang GB;Zeng YQ;Liu PP;Mi TW;Zhang SF;Dai SK;Tang QY;Yang L;Xu YJ;Yan HL;Du HZ;Teng ZQ;Zhou FQ;Liu CM
组蛋白去甲基化酶UTX介导去除组蛋白H3赖氨酸27（H3 K27 me 3）的抑制性三甲基化，以建立激活大量基因的机械开关。Utx的突变最近被证明与歌舞伎综合征有关，歌舞伎综合征是一种罕见的先天性异常综合征，伴有痴呆。然而，它在大脑中的生物学功能在很大程度上是未知的。在这里，我们观察到Utx的缺失导致小鼠的焦虑样行为增加和空间学习和记忆受损。海马中Utx的缺失导致微兴奋性突触后电流的长时程增强和振幅降低、树突发育异常和突触形成缺陷。转录谱分析表明，Utx调节的一个子集的基因，参与调节树突形态，突触传递和认知。具体地，Utx缺失破坏神经递质5-羟色胺受体5 B（Htr 5 b）的表达。新生海马神经元中Htr 5 b表达的恢复挽救了Utx消融的神经元形态缺陷。因此，我们提供的证据表明，UTX在调节突触传递和认知行为中起着至关重要的作用。像我们这样的UTX cKO小鼠模型为研究歌舞伎综合征病因学的潜在机制提供了有价值的手段。
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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影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
5
作者：
COSTALL, B;DOMENEY, AM;EGLEN, RM
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EGLEN, RM
影响因子：
9.8
作者：
Lederer, Damien;Grisart, Bernard;Verellen-Dumoulin, Christine
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影响因子：
4.8
作者：
Etchegaray, Jean-Pierre;Yang, Xiaoming;Reppert, Steven M.
通讯作者：
Reppert, Steven M.
影响因子：
64.8
作者：
LIAO, DZ;HESSLER, NA;MALINOW, R
通讯作者：
MALINOW, R