Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.
Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.
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DOI：
10.3390/biomedicines10081946
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发表时间：
2022-08-11
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
即早基因Arc是突触功能的主要调节者，也是记忆巩固的关键决定因素。在这里，我们表明，弧与动态染色质相互作用，并密切相关的组蛋白标记的活性增强子和转录在培养的大鼠海马神经元。这两种组蛋白修饰，H3K27Ac和H3K9Ac，最近已被证明在晚发性阿尔茨海默病（AD）中上调。当使用短发夹RNA阻止由药理学网络激活引起的Arc诱导时，超过1900个基因的表达谱发生了改变，其中包括与突触功能、神经元可塑性、内在兴奋性和信号通路相关的基因。有趣的是，大约100个弧依赖基因与AD的病理生理学相关。当在HEK293T细胞中诱导内源性Arc表达时，许多神经元基因的转录增加，表明Arc可以在没有激活的信号传导通路的情况下控制表达。两者合计，这些数据建立弧作为一个主调节神经元活性依赖性基因表达，并表明它在AD的病理生理学中起着重要的作用。
The immediate early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Here, we show that Arc interacts with dynamic chromatin and closely associates with histone markers for active enhancers and transcription in cultured rat hippocampal neurons. Both these histone modifications, H3K27Ac and H3K9Ac, have recently been shown to be upregulated in late-onset Alzheimer’s disease (AD). When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes, which included genes associated with synaptic function, neuronal plasticity, intrinsic excitability, and signalling pathways. Interestingly, about 100 Arc-dependent genes are associated with the pathophysiology of AD. When endogenous Arc expression was induced in HEK293T cells, the transcription of many neuronal genes was increased, suggesting that Arc can control expression in the absence of activated signalling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and suggest that it plays a significant role in the pathophysiology of AD.
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影响因子：
15.1
作者：
Abdul-Hay SO;Sahara T;McBride M;Kang D;Leissring MA
通讯作者：
Leissring MA
染色质物理拓扑，分形结构和基因表达之间的全球关系。
影响因子：
4.6
作者：
Almassalha LM;Tiwari A;Ruhoff PT;Stypula-Cyrus Y;Cherkezyan L;Matsuda H;Dela Cruz MA;Chandler JE;White C;Maneval C;Subramanian H;Szleifer I;Roy HK;Backman V
通讯作者：
Backman V
影响因子：
3.6
作者：
Tea JS;Luo L
通讯作者：
Luo L
影响因子：
15.1
作者：
Allen M;Zou F;Chai HS;Younkin CS;Miles R;Nair AA;Crook JE;Pankratz VS;Carrasquillo MM;Rowley CN;Nguyen T;Ma L;Malphrus KG;Bisceglio G;Ortolaza AI;Palusak R;Middha S;Maharjan S;Georgescu C;Schultz D;Rakhshan F;Kolbert CP;Jen J;Sando SB;Aasly JO;Barcikowska M;Uitti RJ;Wszolek ZK;Ross OA;Petersen RC;Graff-Radford NR;Dickson DW;Younkin SG;Ertekin-Taner N
通讯作者：
Ertekin-Taner N
影响因子：
7.2
作者：
Alberini, Cristina M.;Kandel, Eric R.
通讯作者：
Kandel, Eric R.