The neuroplasticity-associated Arc gene is a direct transcriptional target of early growth response (Egr) transcription factors
The neuroplasticity-associated Arc gene is a direct transcriptional target of early growth response (Egr) transcription factors
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DOI：
10.1128/mcb.25.23.10286-10300.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Tourtellotte, WG
中科院分区：
文献类型：
--
作者：
Li, L;Carter, J;Tourtellotte, WG
早期生长反应转录因子（Early growth response，Egr）是突触活性诱导的即早基因（immediate early genes，IEGs），调控与学习记忆相关的突触可塑性，但其调控的靶基因尚不清楚。特别是，Egr 1对于晚期长时程增强（L-LTP）的持续性，对于海马依赖性长期记忆的形成，以及对于先前建立的记忆的重新巩固是必不可少的。在这里，我们表明，Egr 1和Egr 3直接调节可塑性相关的活性调节的细胞色素相关（Arc）基因，突触活性诱导的效应分子，这也是需要L-LTP和海马依赖性学习和记忆处理。此外，缺乏Egr 1和Egr 3的小鼠在神经元亚群中缺乏Arc蛋白，而缺乏Egr 1和Egr 3的小鼠在所有神经元中都缺乏Arc。因此，Egr 1和Egr 3可以通过直接调节Arc及其在最近激活的突触中介导的可塑性机制来间接调节突触可塑性。
Early growth response (Egr) transcription factors (Egr1 to Egr4) are synaptic activity-inducible immediate early genes (IEGs) that regulate some aspects of synaptic plasticity-related to learning and memory, yet the target genes regulated by them are unknown. In particular, Egr1 is essential for persistence of late-phase long-term potentiation (L-LTP), for hippocampus-dependent long-term memory formation, and for reconsolidation of previously established memories. Here, we show that Egr1 and Egr3 directly regulate the plasticity-associated activity-regulated cytoskeletal-related (Arc) gene, a synaptic activity-induced effector molecule which is also required for L-LTP and hippocampus-dependent learning and memory processing. Moreover, Egr1-deficient and Egr3-deficient mice lack Arc protein in a subpopulation of neurons, while mice lacking both Egr1 and Egr3 lack Arc in all neurons. Thus, Egr1 and Egr3 can indirectly modulate synaptic plasticity by directly regulating Arc and the plasticity mechanisms it mediates in recently activated synapses.