MYOSIN LIGHT CHAIN ENHANCER ACTIVATES MUSCLE-SPECIFIC, DEVELOPMENTALLY REGULATED GENE-EXPRESSION IN TRANSGENIC MICE
MYOSIN LIGHT CHAIN ENHANCER ACTIVATES MUSCLE-SPECIFIC, DEVELOPMENTALLY REGULATED GENE-EXPRESSION IN TRANSGENIC MICE
复制标题
DOI：
10.1073/pnas.86.20.7780
复制
发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
MERLIE, JP
中科院分区：
文献类型：
--
作者：
ROSENTHAL, N;KORNHAUSER, JM;MERLIE, JP
大鼠肌球蛋白轻链（MLC）1/3基因位点含有一个有效的肌肉特异性增强子，位于编码区下游，距离MLC 1转录起始位点>24个酶。为了评估这种增强子在发育过程中激活MLC表达中的作用，产生了转基因小鼠，其携带多个拷贝的MLC 1启动子-氯霉素乙酰转移酶（CAT）转录单位，该转录单位连接到包括增强子的基因组片段。在四种小鼠品系中检测到CAT表达，骨骼肌中的CAT表达比其他组织高1000倍。这些动物出生前4天内源性MLC 1转录的激活反映在CAT转基因表达的开始。本研究确定了在适当的胎儿阶段激活21-腺苷酸酶MLC 1/3位点所必需的转录控制元件，并表明MLC增强子足以诱导MLC 1启动子在骨骼肌细胞中的发育调控表达。
The rat myosin light chain (MLC)1/3 gene locus contains a potent muscle-specific enhancer, located down-stream of the coding region, >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.