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 ot her organs, This tissue-specific expression might be regulated by nega tive elements as well as positive elements, such as tissue-specific en hancers, To investigate the repression mechanisms of this gene in orga ns other than the brain, transfection experiments were performed by us ing various deletion mutants, Interestingly, a 25 x CTG repeat in the promoter region seemed to contribute to the repression activity, Moreo ver, the repression activity of this 25 x CTG repeat was also observed in various promoters and in a direction and position independent mann er, indicating that this element could act as a silencer. However, no binding protein was detected by gel-shift and footprint analyses. Thes e 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 C TG repeat functions as a general silencer in many genes.