Redundant Domains Contribute to the Transcriptional Activity of the Thyroid Transcription Factor 1

Abstract

The thyroid transcription factor 1 (TTF-1) is a homeodomain-containing protein implicated in the activation of thyroid-specific gene expression. Here we report that TTF-1 is capable of activating transcription from thyroglobulin and, to a lesser extent, thyroperoxidase gene promoters in nonthyroid cells. Full transcriptional activation of the thyroglobulin promoter by TTF-1 requires the presence of at least two TTF-1 binding sites. TTF-1 activates transcription via two functionally redundant transcriptional activation domains that as suggested by competition experiments, could use a common intermediary factor.

Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

“…7A) was used in these experiments. The ⌬G-21 fusion protein was more potent than ⌬G-13 to transactivate the pG5Luc reporter as previously shown (26). Interestingly, while cotransfection with DREAM totally blocked ⌬G-21 transactivation it did not affect the activity of ⌬G-13 (Fig.…”

“…As a result, DREAM blocks TTF-1-mediated transactivation of Tg gene expression. The N-terminal region of TTF-1 contains the main activation domain (26,38) and is responsible for the interaction between TTF-1 and Pax-8 that is essential for the activation of Tg gene expression (39). In addition, the N-terminal part of TTF-1 is required for the interaction between TTF-1 and co-activators like TBP, p300, and TAF (21,38,40).…”

“…RSV-Luc and pRL-CMV were used to correct for transfection efficiency. Plasmids encoding wild-type TTF-1 (25), TTF-1⌬3 and TTF-⌬14 deletions, and Gal4-TTF-1 constructs have been previously described (26), as well as the plasmid pCMV-Pax-8 (27). For analysis of DREAM activity we used expression vectors containing wild-type DREAM (wtDREAM) (17) and different DREAM mutants; DREAM 2,3,4EF-hand mutant (EFmDREAM), contains mutations in three of the four EF-hand motifs resulting in a protein insensitive to calcium (17).…”

Protein Kinase A Activation of the Surfactant Protein B Gene Is Mediated by Phosphorylation of Thyroid Transcription Factor 1

“…5B, lane d). These results demonstrated that the PKA phosphorylation site was located near the NH 2 terminus of TTF-1 in a region associated with transactivation activity (24).…”

“…Gene-targeted deletion of the mouse TTF-1 gene (titf1) caused severe pulmonary hypoplasia (12). TTF-1 also plays a role in gene expression in the thyroid gland, activating thyroperoxidase and thyroglobulin gene transcription (23,24,32). Because of the role of TTF-1 in surfactant protein gene expression and previous studies supporting the role of cyclic AMP in lung epithelial differentiation and function, the present study was designed to assess the potential interactions between cAMP-dependent pathways and the activity of TTF-1.…”