Opposing early inhibitory and late stimulatory effects of insulin-like growth factor-I on myogenin gene transcription
✍ Scribed by Saleh Adi; Zhao-Qin Cheng; Pei-Lin Zhang; Nan Yan Wu; Synthia H. Mellon; Stephen M. Rosenthal
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 163 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Insulinlike growth factor s (IGFs) stimulate skeletal muscle cell differentiatio n in association with an increase in the mRNA of myogenin, a member of the MyoD family of skeletal muscle-specific transcriptio n factor s that plays an essential role in the differentiatio n process. However, this is a relatively late effect , requiring treatmen t periods of Ͼ24 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 IGF-I inhibits myogenin gene transcriptio n byϾ80% but has no effect on myogenin mRNA stability. Similarly, in the first 24 h, IGF-I markedly inhibits myogenin promoter activity; the sequence Ϫ145 to Ϫ9 of the myogenin gene is sufficient to confer this inhibitory effect of IGF-I. In contrast , 48 h of treatmen t with IGF-I results in an increase in myogenin promoter activity that parallels the increase in myogenin steady-stat e mRNA. This increase in promoter activity is completely prevented in construct s lacking the sequenceϪ1,565 to Ϫ375 of the myogenin gene. These data indicate that the early inhibitory and late stimulator y effect s of IGF-I on myogenin expression are mediated at the level of transcription, and that these time-dependent, opposing effect s of IGF-I on myogenin transcriptio n are mediated by distinct regions of the myogenin gene. To our knowledge, this is the first demonstratio n of a gene whose promoter activity is initially inhibited and subsequently stimulated by IGF-I.