Neuronal activity-regulated gene expression plays a crucial role in sculpting neural circuits that underpin adaptive brain function. Transcriptional enhancers are now recognized as key components of gene regulation that orchestrate spatiotemporally precise patterns of gene transcription. We propose that the dynamics of enhancer activation uniquely position these genomic elements to finely tune activity-dependent cellular plasticity. Enhancer specificity and modularity can be exploited to gain selective genetic access to specific cell states, and the precise modulation of target gene expression within restricted cellular contexts enabled by targeted enhancer manipulation allows for fine-grained evaluation of gene function. Mounting evidence also suggests that enduring stimulus-induced changes in enhancer states can modify target gene activation upon restimulation, thereby contributing to a form of cell-wide metaplasticity. We advocate for focused exploration of activity-dependent enhancer function to gain new insight into the mechanisms underlying brain plasticity and cognitive dysfunction.

中文翻译：

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神经元增强子微调自适应回路可塑性


神经元活动调节的基因表达在塑造支撑适应性大脑功能的神经回路中起着至关重要的作用。转录增强子现在被认为是基因调控的关键组成部分，可以协调基因转录的时空精确模式。我们提出增强子激活的动力学独特地定位这些基因组元件，以微调活性依赖性细胞可塑性。可以利用增强子的特异性和模块化来获得对特定细胞状态的选择性遗传访问，并且通过靶向增强子操作实现的受限细胞环境中靶基因表达的精确调节允许对基因功能进行精细评估。越来越多的证据还表明，持久的刺激诱导的增强子状态变化可以在再刺激时改变靶基因激活，从而促进一种全细胞转移。我们倡导集中探索活动依赖性增强子功能，以获得对大脑可塑性和认知功能障碍机制的新见解。