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.