The transfection and overexpression of the cDNA encoding the thyroid hormone receptor (TR) in mammalian cells has shed light into several aspects of the function and biological characteristics of the TR in cells. Using this method, thyroid hormone and TR-responsive genes and response elements were identified. As well, the diversity of TR binding sequences and the effect of heterodimerization with retinoid x receptor (RXR) were elucidated. Furthermore, the functional domains of the TR, its activation domain, hormone-dependent transactivation function, nuclear localization, dimerization properties, and silencing domain could be identified and characterized (Fig. 1), for (reviews see refs. 1-3). The identification and analysis of functional domains of TR was accomplished mostly by generating fusion proteins of TR parts to a heterologous DNA-binding domain (DBD), such as that of the GAL4-DBD. These fusion proteins permitted the determination of amino acids required for a specific receptor function and allowed the dissection and separate characterization of the various functions of TR (4,5).