Potential mechanisms of negative regulation of gene expression by TH. (a) TH binding to TR triggers a switch from coactivator to corepressor binding on an nTRE on DNA. This mechanism absolutely requires direct DNA binding by TR. (b) TH binding to TR triggers a switch from coactivator to corepressor binding in the context of a protein-protein interaction, shown here with the AP-1 complex (jun/fos). (c) TH binding to TR recruits coactivator away from a DNA-bound factor such as AP-1.