Looking for the Mechanism of Action of Thyroid Hormone
Figure 2
A representation by Wolffe [8] of how a ligand-activated nuclear receptor could modify the higher-order structure of chromatin. The packaging of DNA into chromatin is visualized in three transcriptionally active states: normal, repressive, and active. In this example, the region of chromatin chosen contains the thyroid hormone receptor (TR)/RXR heterodimer, with or without its ligand triiodothyronine (T3), bound to the thyroid responsive element (TRE) in the target gene. In normal chromatin, histone acetylation is at its basal level and so is the transcriptional activity. In the absence of T3 (as during early stages of development), chromatin exists in its condensed and transcriptionally repressive form whereby the histones are in a largely deacetylated state with no transcription of the TR’s target gene. In the presence of T3, the chromatin is now active with elevated levels of histone acetylation and transcription. The other components are proteins that form “corepressor” and “coactivator” complexes with complexes with the TR/RXR receptor heterodimer. For more details, see [8].
