The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain

The neuron-restrictive silencer element (NRSE) has been identified in several neuronal genes and confers neuron specificity by silencing transcription in nonneuronal cells. NRSE is present in the promoter of the neuronal nicotinic acetylcholine receptor β2-subunit gene that determines its neuron-specific expression in the nervous system. Using transgenic mice, we show that NRSE may either silence or enhance transcription depending on the cellular context within the nervous system. In vitro in neuronal cells, NRSE activates transcription of synthetic promoters when located downstream in the 5′ untranslated region, or at less than 50 bp upstream from the TATA box, but switches to a silencer when located further upstream. In contrast, in nonneuronal cells NRSE always functions as a silencer. Antisense RNA inhibition shows that the NRSE-binding protein REST contributes to the activation of transcription in neuronal cells.

神经元限制性沉默元件（neuron-restrictive silencer element，NRSE）已在多种神经元基因中被鉴定，其可通过在非神经元细胞中沉默转录，赋予相关基因神经元表达特异性。NRSE存在于神经元烟碱型乙酰胆碱受体β2亚基基因的启动子区域，该区域决定了此基因在神经系统内的神经元特异性表达模式。本研究通过转基因小鼠实验证实，NRSE在神经系统中可依据细胞环境的差异，分别发挥转录沉默或转录增强的双重调控功能。在神经元细胞的体外实验体系中，当NRSE位于5'非翻译区（5' untranslated region）下游，或距离TATA盒（TATA box）不足50 bp的上游位置时，可激活合成型启动子的转录；但若其位于更上游的区域，则会切换为转录沉默子。与之形成鲜明对比的是，在非神经元细胞中，NRSE始终仅发挥转录沉默子的功能。反义RNA抑制实验结果显示，NRSE结合蛋白REST（NRSE-binding protein REST）参与了神经元细胞内的转录激活过程。