Thyroid hormone action: a binding contract

Abstract

Thyroid hormones are critical for differentiation, growth, and metabolism. A new study investigating the biological role of the TH receptor TR-beta has demonstrated that DNA binding is critical for most of its functions, but also suggests that novel mechanisms independent of DNA binding may contribute to regulation of auditory function by TR-beta.

Figure 1

Paradigm for positive regulation of gene expression by TH. TH binding to TR triggers a switch from corepressor (CoR) to coactivator (CoA) binding on a TRE on DNA.

Figure 2

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.