...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene.
【24h】

A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene.

机译：ras依赖的途径废除了肌肉肌酸激酶基因上游的肌肉特异性增强子的活性。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Differentiation of skeletal myoblasts is accompanied by induction of a series of tissue-specific genes whose products are required for the specialized functions of the mature muscle fiber. The program for myogenic differentiation is subject to negative control by several peptide growth factors and by the products of mutationally activated ras oncogenes, which persistently activate intracellular cascades normally triggered by specific growth factors. Previously, we reported that induction of the muscle creatine kinase (mck) gene during myogenesis was dependent on a distal upstream enhancer that cooperated with a proximal promoter to direct high levels of expression in developing muscle cells (E. A. Sternberg, G. Spizz, W. M. Perry, D. Vizard, T. Weil, and E. N. Olson, Mol. Cell. Biol. 8:2896-2909). To investigate the mechanisms whereby ras blocks the induction of muscle-specific genes, we have examined the ability of mck 5' regulatory elements to direct expression of the linked reporter gene for chloramphenicol acetyltransferase (cat) in C2 myoblasts bearing mutant N-ras and H-ras oncogenes. In this paper we report that expression of activated ras alleles abolishes activity of the mck upstream enhancer but does not affect the activity of the mck promoter. The ability of ras to repress the expression of mck-cat fusion genes that have been transfected either transiently or stably into myoblasts suggests that ras may exert its effects on muscle-specific genes through mechanisms independent of chromatin configurations or DNA methylation. These results also suggest that ras blocks establishment of the myogenic phenotype by preventing the accumulation of regulatory factors required for transcriptional induction of muscle-specific genes.
机译：骨骼肌成肌细胞的分化伴随着一系列组织特异性基因的诱导，其产物是成熟肌纤维的特殊功能所必需的。用于肌原性分化的程序受到几种肽生长因子和突变激活的ras癌基因产物的负控制，后者持续激活通常由特定生长因子触发的细胞内级联反应。以前，我们报道了在肌生成过程中肌酸肌酸激酶（mck）基因的诱导依赖于远端上游增强子，该增强子与近端启动子协同作用以指导发育中的肌肉细胞中高水平的表达（EA Sternberg，G。Spizz，WM Perry ，D.Vizard，T.Weil，和EN Olson，Mol.Cell.Biol.8：2896-2909）。为了研究ras阻断肌肉特异性基因诱导的机制，我们研究了mck 5'调控元件指导氯霉素乙酰转移酶（cat）的相关报道基因在携带突变N-ras和H的C2成肌细胞中表达的能力。 -ras癌基因。在本文中，我们报道了活化的ras等位基因的表达消除了mck上游增强子的活性，但不影响mck启动子的活性。 ras抑制已经被瞬时或稳定转染到成肌细胞中的mck-cat融合基因表达的能力表明ras可以通过独立于染色质构型或DNA甲基化的机制对肌肉特异性基因发挥作用。这些结果还表明，ras通过阻止积累肌肉特异性基因的转录诱导所需的调节因子而阻止了肌原性表型的建立。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号