Merlie J P, Mudd J, Cheng T C, Olson E N
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1994 Jan 28;269(4):2461-7.
Several genes expressed in skeletal muscle are transcriptionally repressed by electrical activity arising from motor innervation and are rapidly induced following denervation. Among these are genes encoding the subunits of the nicotinic acetylcholine receptor (AChR) and the myogenic helix-loop-helix protein myogenin, which activates muscle-specific genes. To understand how electrical activity arising from motor innervation is converted into a transcriptional response, we have attempted to localize cis-acting sequences in the AChR alpha subunit and myogenin genes sufficient to direct activity-dependent transcription. Here we show that an 111-base pair and a 335-base pair region from the promoters of the AChR alpha subunit and myogenin genes, respectively, can confer activity-dependent regulation to a linked reporter gene in transgenic mice. The presence of binding sites for myogenic helix-loop-helix proteins in both of these regulatory regions is consistent with the hypothesis that these myogenic regulators serve as nuclear targets for the signaling cascade through which motor innervation leads to changes in gene transcription in skeletal muscle.
骨骼肌中表达的几个基因会受到运动神经支配产生的电活动的转录抑制，并且在去神经支配后会迅速被诱导。其中包括编码烟碱型乙酰胆碱受体（AChR）亚基的基因和激活肌肉特异性基因的生肌螺旋-环-螺旋蛋白肌细胞生成素。为了了解运动神经支配产生的电活动是如何转化为转录反应的，我们试图在AChRα亚基和肌细胞生成素基因中定位足以指导活性依赖转录的顺式作用序列。在此我们表明，分别来自AChRα亚基和肌细胞生成素基因启动子的一个111碱基对区域和一个335碱基对区域，可以赋予转基因小鼠中一个相连的报告基因活性依赖的调控。这两个调控区域中均存在生肌螺旋-环-螺旋蛋白的结合位点，这与以下假设一致，即这些生肌调节因子作为信号级联的核靶点，通过该信号级联，运动神经支配导致骨骼肌中基因转录的变化。
