Opposing early inhibitory and late stimulatory effects of insulin-like growth factor-I on myogenin gene transcription
Opposing early inhibitory and late stimulatory effects of insulin-like growth factor-I on myogenin gene transcription
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DOI：
10.1002/1097-4644(20000915)78:4
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发表时间：
2000-01-01
影响因子：
4
通讯作者：
Rosenthal, SM
中科院分区：
文献类型：
--
作者：
Adi, S;Cheng, ZQ;Rosenthal, SM
Insulinlike growth factors (IGFs) stimulate skeletal muscle cell differentiation in association with an increase in the mRNA of myogenin, a member of the MyoD family of skeletal muscle-specific transcription factors that plays an essential role in the differentiation process. However, this is a relatively late effect, requiring treatment periods of >24 h. In contrast, IGFs initially inhibit skeletal muscle cell differentiation, associated with a marked reduction in myogenin mRNA. The mechanisms by which IGF-I initially inhibits and subsequently stimulates myogenin expression are unknown. In the first 24 h, we find that ICF-I inhibits myogenin gene transcription by >80% but has no effect on myogenin mRNA stability. Similarly, in the first 24 h, IGF-I markedly inhibits myogenin promoter activity; the sequence -145 to -9 of the myogenin gene is sufficient to confer this inhibitory effect of IGF-I. In contrast, 48 h of treatment with IGF-I results in an increase in myogenin promoter activity that parallels the increase in myogenin steady-state mRNA. This increase in promoter activity is completely prevented in constructs lacking the sequence -1,565 to -375 of the myogenin gene. These data indicate that the early inhibitory and late stimulatory effects of IGF-I on myogenin expression are mediated at the level of transcription, and that these lime-dependent, opposing effects of IGF-I on myogenin transcription are mediated by distinct regions of the myogenin gene. To our knowledge, this is the first demonstration of a gene whose promoter activity is initially inhibited and subsequently stimulated by ICF-I. J. Cell. Biochem. 78:617-626, 2000. (C) 2000 Wiley-Liss, Inc.
