2 SEPARATE NCOR (NUCLEAR RECEPTOR COREPRESSOR) INTERACTION DOMAINS MEDIATE COREPRESSOR ACTION ON THYROID-HORMONE RESPONSE ELEMENTS

The nuclear corepressor (NCoR) binds to the thyroid hormone receptor ( TR) in the absence of ligand. NCoR-TR interactions are mediated by two interaction domains in the C-terminal portion of NCoR, Binding of NCo R to TR results in ligand-independent repression on positive thyroid h ormone response elements. The interactions between NCoR interaction do mains and TR on DNA response elements, however, have not been well cha racterized. We have found that both interaction domains are capable of binding TR on thyroid hormone response elements. In addition, the NCo R interaction domains interact much more strongly with the TR than tho se present in the silencing mediator of retinoic acid and TRs (SMRT). Furthermore, deletion of either NCoR interaction domain does not signi ficantly impair ligand-independent effects on positive or negative thy roid hormone response elements. Finally, both NCoR interaction domains appear to preferentially bind TR homodimer over TR-retinoid X recepto r heterodimer in electrophoretic mobility shift assays. These data sug gest that either NCoR interaction domain is capable of mediating the l igand-independent effects of TR on positive and negative thyroid hormo ne response elements.