Transcriptional repression of human insulin-like growth factor-II P4 promoter by Wilms' tumor suppressor WT1.
The Wilms' tumor suppressor gene wt1 encodes a zinc finger-containing protein that binds to the same DNA sequence as Egr-1, a mitogen-inducible immediate-early gene product that activates transcription. In this study, we investigated whether the human insulin-like growth factor-II (IGF-II) P4 promoter might be a target for transcriptional repression mediated by WT1. Using constructs of the IGF-II P4 promoter linked to the chloramphenicol acetyltransferase gene, we have demonstrated that the WT1 protein represses expression of the IGF-II gene through a GCGGGGGAG response element spanning nucleotides -87 to -65 of the IGF-II P4 promoter. Conversely, we have shown that the Egr-1 activates transcription of the IGF-II gene through the same response element. WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the IGF-II promoter 4 in gel mobility-shift assays. These findings demonstrate the importance of the WT1/Egr-1 consensus element for the expression of the IGF-II gene in response to positive or negative transcription signals.
Lee
Y I
YI
Biomedical Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Korea.
Kim
S J
SJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D025721:WT1 Proteins; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D007335:Insulin-Like Growth Factor II; D004247:DNA