摘要

       活动调节基因 (ARG) 对神经元功能（如长期记忆）很重要，并且在哺乳动物中得到了很好的表征，但在其他模式生物（如果蝇）中的研究却很少。在这里，我们用不同的范式刺激果蝇神经元，并使用来自大脑和排序神经元的高通量测序识别 ARG：它们包括一组狭窄的昼夜节律神经元以及多巴胺能神经元。令人惊讶的是，许多 ARG 特定于刺激范式，并且非常特定于神经元类型。此外，与哺乳动物立即早期基因 (IEG) 不同的是，果蝇 ARG 的基因长度并不短，转录因子功能的富集程度也较低。使用 ATAC 测序的染色质分析表明，ARG 的转录起始位点 (TSS) 不会随着神经放电而改变，但在刺激之前已经可以访问。最后，基于 ARG 中结合位点的富集，我们确定了发射的转录因子介质并创建了神经元活动报告器。

       Activity-regulated genes (ARGs) are important for neuronal functions like long-term memory and are well-characterized in mammals but poorly studied in other model organisms like Drosophila. Here we stimulated fly neurons with different paradigms and identified ARGs using high-throughput sequencing from brains as well as from sorted neurons: they included a narrow set of circadian neurons as well as dopaminergic neurons. Surprisingly, many ARGs are specific to the stimulation paradigm and very specific to neuron type. In addition and unlike mammalian immediate early genes (IEGs), fly ARGs do not have short gene lengths and are less enriched for transcription factor function. Chromatin assays using ATAC-sequencing show that the transcription start sites (TSS) of ARGs do not change with neural firing but are already accessible prior to stimulation. Lastly based on binding site enrichment in ARGs, we identified transcription factor mediators of firing and created neuronal activity reporters.

https://elifesciences.org/articles/19942