J Cell Biochem 2000,
PMID: 10861859
Adi, S; Cheng, Z Q; Zhang, P L; Wu, N Y; Mellon, S H; Rosenthal, S M
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 IGF-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 time-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 IGF-I.
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Text Mining Data
myogenin — insulin-like growth factor-I: "
Opposing early inhibitory and late stimulatory
effects of
insulin-like growth factor-I on
myogenin gene transcription
"
myogenin → IGF-I: "
The mechanisms by which IGF-I initially inhibits and subsequently stimulates myogenin expression are unknown
"
myogenin ⊣ IGF-I: "
In the first 24 h, we find that IGF-I inhibits myogenin gene transcription by > 80 % but has no effect on myogenin mRNA stability
"
myogenin ⊣ IGF-I: "
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
"
myogenin → 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
"
myogenin ⊣ IGF-I: "
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 time dependent, opposing effects of IGF-I on myogenin transcription are mediated by distinct regions of the myogenin gene
"
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