Targeted chromatin binding and histone acetylation in vivo by thyroid hormone receptor during amphibian development

Amphibian metamorphosis is marked by dramatic, thyroid hormone (TH)-induced changes involving gene regulation by TH receptor (TR). It has been postula ted that TR-mediated gene regulation involves chromatin remodeling. In the absence of ligand, TR can repress gene expression by recruiting a histone d eacetylase complex, whereas liganded Tn recruits a histone acetylase comple x for gene activation. Earlier studies have led us to propose a dual functi on model for TR during development. In premetamorphic tadpoles, unliganded Tn represses transcription involving histone deacetylation. During metamorp hosis, endogenous TH allows TR to activate gene expression through histone acetylation. Here using chromatin immunoprecipitation assay, we directly de monstrate TR binding to TH response genes constitutively in vivo in premeta morphic tadpoles. We further show that TH treatment leads to histone deacet ylase release from TH response gene promoters. Interestingly, in whole anim als, changes in histone acetylation show little correlation with the expres sion of TH response genes. On the other hand, in the intestine and tail, wh ere TH response genes are known to be up-regulated more dramatically by TH than in most other organs, we demonstrate that TH treatment induces gene ac tivation and histone H4 acetylation, These data argue for a role of histone acetylation in transcriptional regulation by TRs during amphibian developm ent in some tissues, whereas in others changes in histone acetylation level s may play no or only a minor role, supporting the existence of important a lternative mechanisms in gene regulation by TR.