SYNERGISTIC TRANSCRIPTIONAL ACTIVATION OF THE THYROTROPIN RECEPTOR PROMOTER BY CYCLIC AMP-RESPONSIVE-ELEMENT-BINDING PROTEIN AND THYROID TRANSCRIPTION FACTOR-1

In this study we have investigated the molecular mechanisms involved i n hormonal induction of thyroid-specific transcription of the thyrotro pin receptor (TSHr). A cyclic AMP-responsive element (CRE) has been ch aracterized in the minimal TSHr promoter, and promoter activity shown to be also induced by thyroid transcription factor 1 (TTF-1). We here describe a cooperative effect between TTF-1 and CRE-binding protein on the TSHr promoter. Moreover we have identified a second TTF-1-binding site in the minimal promoter, which does not activate TSHr promoter a ctivity but is required for the co-operative activation of the promote r. This report describes a new aspect of thyroid-specific gene express ion, namely, how a generic extracellular signal can be interpreted in a thyroid-specific way.