EXPRESSION OF THYROID TRANSCRIPTION FACTOR-1 GENE CAN BE REGULATED ATTHE TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS

The complete structure of the gene for thyroid transcription factor 1 (TTF-1), both in rats and humans, has been determined, The rat TTF-1 g ene shows three transcriptional start sites and contains two introns, one of which is alternatively spliced. Nuclear run-on and transient tr ansfection experiments indicate that TTF-1 gene expression can be cont rolled at different levels, Using thyroid and nonthyroid cell lines, i t can be shown that transcriptional mechanisms are involved in control ling thyroid-specific expression of the TTF-1 gene. In contrast, in th yroid cells expressing an activated Ki-ras oncogene, the steady-state level of TTF-1 mRNA is greatly reduced, while transcription of the TTF -1 gene is only moderately affected, suggesting that the accumulation of TTF-1 mRNA can be regulated by a posttranscriptional, Ras-sensitive mechanism.