The purpose of the study described in this report was to define the mechanism underlying quantitatively different thyroid hormone dependent transcriptional activation mediated by thyroid hormone receptors beta-1 and beta-2. We have shown that thyroid hormone receptor beta-2, which differs from beta-1 in the amino acid composition of the amino-terminal region, transactivates malic enzyme thyroid hormone response element (direct repeat + 4) and myelin basic protein thyroid hormone response element (inverted palindrome) poorly, when compared with the transactivation mediated by the beta-1 or alpha-1 receptor. This is not due to different levels of beta-2 and beta-1 expression or the inability of beta-2 to bind to thyroid hormone response element. However, thyroid hormone receptor beta-2 cannot interact with TFIIB as efficiently as the thyroid hormone receptor beta-1. Thus, we concluded that the amino terminal regions of thyroid hormone receptor beta-2 does not affect the receptor binding to thyroid hormone response element; however, it is required in communicating information via TFIIB to the basal transcription machinery, although interactions with other basal transcriptional factors cannot be excluded.
