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.