Expression of thyroid transcription factor 1 gene can be regulated at the transcriptional and posttranscriptional...

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 gene shows three transcriptional start sites and contains two introns, one of which is alternatively spliced. Nuclear run-on and transient transfection experiments indicate that TTF-1 gene expression can be controlled at different levels. Using thyroid and nonthyroid cell lines, it can be shown that transcriptional mechanisms are involved in controlling thyroid-specific expression of the TTF-1 gene. In contrast, in thyroid 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.