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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Regulation of BDNF chromatin status and promoter accessibility in a neural correlate of associative learning
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Regulation of BDNF chromatin status and promoter accessibility in a neural correlate of associative learning

机译：关联学习的神经相关中BDNF染色质状态和启动子可及性的调节

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Brain-derived neurotrophic factor (BDNF) gene expression critically controls learning and its aberrant regulation is implicated in Alzheimer's disease and a host of neurodevelopmental disorders. The BDNF gene is target of known DNA regulatory mechanisms but details of its activity-dependent regulation are not fully characterized. We performed a comprehensive analysis of the epigenetic regulation of the turtle BDNF gene (tBDNF) during a neural correlate of associative learning using an in vitro model of eye blink classical conditioning. Shortly after conditioning onset, the results from ChIP-qPCR show conditioning-dependent increases in methyl-CpG-binding protein 2 (MeCP2) and repressor basic helix-loop-helix binding protein 2 (BHLHB2) binding to tBDNF promoter II that corresponds with transcriptional repression. In contrast, enhanced binding of ten-eleven translocation protein 1 (Tet1), extracellular signal-regulated kinase 1/2 (ERK1/2), and cAMP response element-binding protein (CREB) to promoter III corresponds with transcriptional activation. These actions are accompanied by rapid modifications in histone methylation and phosphorylation status of RNA polymerase II (RNAP II). Significantly, these remarkably coordinated changes in epigenetic factors for two alternatively regulated tBDNF promoters during conditioning are controlled by Tet1 and ERK1/2. Our findings indicate that Tet1 and ERK1/2 are critical partners that, through complementary functions, control learning-dependent tBDNF promoter accessibility required for rapid transcription and acquisition of classical conditioning.
机译：脑源性神经营养因子（BDNF）基因表达关键控制学习，其异常调节与阿尔茨海默氏病和许多神经发育障碍有关。 BDNF基因是已知DNA调节机制的靶标，但是其活性依赖性调节的细节尚未完全表征。我们使用眨眼经典条件的体外模型在联想学习的神经相关过程中对海龟BDNF基因（tBDNF）的表观遗传调控进行了全面分析。调节开始后不久，ChIP-qPCR的结果显示，甲基-CpG结合蛋白2（MeCP2）和阻遏物基本螺旋-环-螺旋结合蛋白2（BHLHB2）与tBDNF启动子II结合的条件依赖性增加抑制。相比之下，十个十一易位蛋白1（Tet1），细胞外信号调节激酶1/2（ERK1 / 2）和cAMP反应元件结合蛋白（CREB）与启动子III的结合增强与转录激活相对应。这些动作伴随着RNA聚合酶II（RNAP II）的组蛋白甲基化和磷酸化状态的快速修饰。重要的是，在调节过程中，两个交替调节的tBDNF启动子在表观遗传因子中的这些显着协调的变化受Tet1和ERK1 / 2控制。我们的发现表明，Tet1和ERK1 / 2是至关重要的伙伴，它们通过互补功能控制快速转录和经典条件获取所需的学习依赖性tBDNF启动子可及性。

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