Characteristics of a negative thyroid hormone response element.

Thyroid hormones may stimulate or repress transcriptional activity depending upon the specific gene. Whereas, a palindromic DNA sequence, TREpal, mediates positive regulation by thyroid hormone, the negative response element (nT3RE) remains undefined. Therefore, we have examined the DNA sequences that mediate the inhibitory effects of thyroid hormone on the transcription of the beta-subunit gene of rat thyrotropin (rTSH beta). In rat pituitary tumor cells (GH3), transient expression of plasmid constructs containing the putative nT3RE of rTSH beta mediated negative regulation by L-triiodothyronine (T3). Since this nT3RE contained sequences which resembled a half-site motif of the consensus T3RE and the idealized palindrome (TREpal), we tested a construct containing this half-site motif in the same cells. T3 decreased the activity of this plasmid. Cotransfection studies in T3-receptor (T3R)-deficient cells indicated that either alpha or beta isoforms of T3R were required for the inhibitory effects of the hormone. Both T3R isomers bind to DNA sequences containing the nT3RE from rTSH beta DNA or the half-site motif of TREpal. In summary, our results show that the repressive properties of T3 are mediated by a nT3RE from rTSH beta. Unexpectedly, this motif resembles a half-site component of TREpal which enhances promoter activity in response to T3.