CTG triplet repeat in mouse growth inhibitory factor/metallothionein III gene promoter represses the transcriptional activity of the heterologous promoters.
Growth inhibitory factor/metallothionein III (GIF/MT-III) is expressed specifically in brain, and neither mRNA nor protein is detected in other organs. This tissue-specific expression might be regulated by negative elements as well as positive elements, such as tissue-specific enhancers. To investigate the repression mechanisms of this gene in organs other than the brain, transfection experiments were performed by using various deletion mutants. Interestingly, a 25 x CTG repeat in the promoter region seemed to contribute to the repression activity. Moreover, the repression activity of this 25 x CTG repeat was also observed in various promoters and in a direction and position independent manner, indicating that this element could act as a silencer. However, no binding protein was detected by gel-shift and footprint analyses. These results strongly suggest that the CTG repeat functions as a negative element, and that this effect is caused by unknown mechanisms, rather than by interactions between specific cis-elements and specific trans-acting factors as reported previously. It is also possible that the CTG repeat functions as a general silencer in many genes.
Imagawa
M
M
Department of Environmental Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Ishikawa
Y
Y
Shimano
H
H
Osada
S
S
Nishihara
T
T
D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D000090023:Metallothionein 3; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins