| First Author | Gordon DF | Year | 1997 |
| Journal | J Biol Chem | Volume | 272 |
| Issue | 39 | Pages | 24339-47 |
| PubMed ID | 9305891 | Mgi Jnum | J:43153 |
| Mgi Id | MGI:1097213 | Doi | 10.1074/jbc.272.39.24339 |
| Citation | Gordon DF, et al. (1997) Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter. J Biol Chem 272(39):24339-47 |
| abstractText | The molecular determinants governing cell-specific expression of the thyrotropin (TSH) beta-subunit gene in pituitary thyrotropes are not well understood. The P1 region of the mouse TSHbeta promoter (-133 to -88) region interacts with Pit-1 and an additional 50-kDa factor at an adjacent site that resembles a consensus GATA binding site. Northern and Western blot assays demonstrated the presence of GATA-2 transcripts and protein in TtT-97 thyrotropic tumors. In electrophoretic mobility shift assays, a comigrating complex was observed with both TtT-97 nuclear extracts and GATA-2 expressed in COS cells. The complex demonstrated binding specificity to the P1 region DNA probe and could be disrupted by a GATA-2 antibody. When both Pit-1 and GATA-2 were combined, a slower migrating complex, indicative of a ternary protein-DNA interaction was observed. Cotransfection of both Pit-1 and GATA-2 into CV-1 cells synergistically stimulated mouse TSHbeta promoter activity 8.5-fold, while each factor alone had a minimal effect. Mutations that abrogated this functional stimulatory effect mapped to the P1 region. Finally, we show that GATA-2 directly interacts with Pit-1 in solution. In summary, these data demonstrate functional synergy and physical interaction between homeobox and zinc finger factors and provide insights into the transcriptional mechanisms of thyrotrope-specific gene expression. |
