摘要

       基因转录是建立和维持长期增强 (LTP) 持久形式所必需的。然而，支持 LTP 的转录组及其相关分子程序尚不清楚。本研究的目的是鉴定受 LTP 诱导调节的活性调节基因 (ARG) 及其分子途径，并研究协调 ARG 转录的基因组机制。我们对小鼠齿状回进行了时间进程 DNA 微阵列分析，以确定响应 LTP 诱导强直刺激的 ARG 的时间基因组表达谱。我们的研究发现了调节各种细胞过程的 ARG，包括突触的结构和功能，并概述了可能对 LTP 很重要的动态分子程序。令人惊讶的是，我们发现 ARGs 聚集在染色体上，并且 ARG 簇在进化过程中是保守的。尽管同一簇中的 ARGs 具有明显不同的分子特性，但它们通过调节 LTP 在功能上相关。此外，特定簇中的 ARG 由 cAMP 反应元件结合蛋白共同调节。我们建议染色体聚类为协调参与 LTP 的 ARG 的转录提供了基因组机制。

       Gene transcription is required for establishing and maintaining the enduring form of long term potentiation (LTP). However, the transcriptome and its associated molecular programs that support LTP are not well understood. The purpose of this study was to identify activity-regulated genes (ARGs) and their molecular pathways that are modulated by LTP induction and to investigate the genomic mechanism for coordinating the transcription of ARGs. We performed time course DNA microarray analyses on the mouse dentate gyrus to determine the temporal genomic expression profiles of ARGs in response to LTP-inducing tetanic stimulation. Our studies uncovered ARGs that regulate various cellular processes, including the structure and function of the synapse, and offered an overview of the dynamic molecular programs that are probably important for LTP. Surprisingly, we found that ARGs are clustered on chromosomes, and ARG clusters are conserved during evolution. Although ARGs in the same cluster have apparently different molecular properties, they are functionally correlated by regulating LTP. In addition, ARGs in specific clusters are co-regulated by the cAMP-response element-binding protein. We propose that chromosomal clustering provides a genomic mechanism for coordinating the transcription of ARGs involved in LTP.

https://www.sciencedirect.com/science/article/pii/S0021925819339250