Thyroid hormone receptor actions on transcription in amphibia: The roles of histone modification and chromatin disruption

Thyroid hormone (T3) plays diverse roles in adult organ function and during vertebrate development. The most important stage of mammalian development affected by T3 is the perinatal period when plasma T3 level peaks. Amphibian metamorphosis resembles this mammalian postembryonic period and is absolutely dependent on T3. The ability to easily manipulate this process makes it an ideal model to study the molecular mechanisms governing T3 action during vertebrate development. T3 functions mostly by regulating gene expression through T3 receptors (TRs). Studies in vitro, in cell cultures and reconstituted frog oocyte transcription system have revealed that TRs can both activate and repress gene transcription in a T3-dependent manner and involve chromatin disruption and histone modifications. These changes are accompanied by the recruitment of diverse cofactor complexes. More recently, genetic studies in mouse and frog have provided strong evidence for a role of cofactor complexes in T3 signaling in vivo. Molecular studies on amphibian metamorphosis have also revealed that developmental gene regulation by T3 involves histone modifications and the disruption of chromatin structure at the target genes as evidenced by the loss of core histones, arguing that chromatin remodeling is an important mechanism for gene activation by liganded TR during vertebrate development.