Rosenthal N, Kornhauser J M, Donoghue M, Rosen K M, Merlie J P
Department of Biochemistry, Boston University School of Medicine, MA 02118.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7780-4. doi: 10.1073/pnas.86.20.7780.
The rat myosin light chain (MLC)1/3 gene locus contains a potent muscle-specific enhancer, located downstream of the coding region, greater than 24 kilobases away from the MLC1 transcription start site. To assess the role of this enhancer in the activation of MLC expression during development, transgenic mice were generated carrying multiple copies of a MLC1 promoter-chloramphenicol acetyltransferase (CAT) transcription unit linked to a genomic fragment including the enhancer. CAT expression was detected in four mouse lines, up to 1000-fold higher in skeletal muscles than in other tissues. Activation of endogenous MLC1 transcription in these animals 4 days before birth was reflected in the onset of CAT transgene expression. This study identifies the transcriptional control elements necessary to activate the 21-kilobase MLC1/3 locus at the appropriate fetal stage and indicates that the MLC enhancer is sufficient to induce developmentally regulated expression from the MLC1 promoter exclusively in skeletal muscle cells.
大鼠肌球蛋白轻链（MLC）1/3基因座包含一个强大的肌肉特异性增强子，位于编码区下游，距离MLC1转录起始位点超过24千碱基。为了评估该增强子在发育过程中激活MLC表达的作用，构建了转基因小鼠，其携带与包含该增强子的基因组片段相连的多个拷贝的MLC1启动子-氯霉素乙酰转移酶（CAT）转录单元。在四个小鼠品系中检测到了CAT表达，在骨骼肌中的表达比在其他组织中高1000倍。出生前4天这些动物体内内源性MLC1转录的激活反映在CAT转基因表达的开始。这项研究确定了在适当的胎儿阶段激活21千碱基的MLC1/3基因座所需的转录控制元件，并表明MLC增强子足以仅在骨骼肌细胞中诱导从MLC1启动子进行发育调控的表达。
