Laboratory of Neurobiology, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle Park, North Carolina, USA.
Nat Neurosci. 2011 May 29;14(7):848-56. doi: 10.1038/nn.2839.
Transcription of immediate early genes (IEGs) in neurons is highly sensitive to neuronal activity, but the mechanism underlying these early transcription events is largely unknown. We found that several IEGs, such as Arc (also known as Arg3.1), are poised for near-instantaneous transcription by the stalling of RNA polymerase II (Pol II) just downstream of the transcription start site in rat neurons. Depletion through RNA interference of negative elongation factor, a mediator of Pol II stalling, reduced the Pol II occupancy of the Arc promoter and compromised the rapid induction of Arc and other IEGs. In contrast, reduction of Pol II stalling did not prevent transcription of IEGs that were expressed later and largely lacked promoter-proximal Pol II stalling. Together, our data strongly indicate that the rapid induction of neuronal IEGs requires poised Pol II and suggest a role for this mechanism in a wide variety of transcription-dependent processes, including learning and memory.
神经元中早期基因（IEGs）的转录对神经元活动高度敏感，但这些早期转录事件的机制在很大程度上尚不清楚。我们发现，几种 IEG，如 Arc（也称为 Arg3.1），通过 RNA 聚合酶 II（Pol II）在转录起始位点下游的暂停，处于几乎即时转录的状态。通过 RNA 干扰负延伸因子（Pol II 暂停的介质）进行耗竭，降低了 Arc 启动子的 Pol II 占有率，并损害了 Arc 和其他 IEG 的快速诱导。相比之下，减少 Pol II 暂停并不会阻止表达较晚且很大程度上缺乏启动子近端 Pol II 暂停的 IEG 的转录。总之，我们的数据强烈表明，神经元 IEG 的快速诱导需要暂停的 Pol II，并表明该机制在包括学习和记忆在内的多种转录依赖过程中发挥作用。
