CHARACTERISTICS OF A NEGATIVE THYROID-HORMONE RESPONSE ELEMENT

Thyroid hormones may stimulate or repress transcriptional activity dep ending upon the specific gene. Whereas, a palindromic DNA sequence, TR Epal, mediates positive regulation by thyroid hormone, the negative re sponse element (nT(3)RE) remains undefined. Therefore, we have examine d the DNA sequences that mediate the inhibitory effects of thyroid hor mone on the transcription of the beta-subunit gene of rat thyrotropin (rTSH beta). In rat pituitary tumor cells (GH(3)), transient expressio n of plasmid constructs containing the putative nT(3)RE of rTSH beta m ediated negative regulation by L-triiodothyronine (T-3). Since this nT (3)RE contained sequences which resembled a half-site motif of the con sensus T(3)RE and the idealized palindrome (TREpal), we tested a const ruct containing this half-site motif in the same cells. T-3 decreased the activity of this plasmid. Cotransfection studies in T-3-receptor ( T(3)R)-deficient cells indicated that either alpha or beta isoforms of T(3)R were required for the inhibitory effects of the hormone. Both T (3)R isomers bind to DNA sequences containing the nT(3)RE from rTSH be ta DNA or the half-site motif of TREpal. In summary, our results show that the repressive properties of T-3 are mediated by a nT(3)RE from r TSH beta. Unexpectedly, this motif resembles a half-site component of TREpal which enhances promoter activity in response to T-3.