Abstract
Thyroid hormone (T3) plays important roles in regulating vertebrate development and pathogenesis. We are using T3‐ dependent Xenopus metamorphosis as a model to study how T3 regulates transcription during development. T3 exerts its metamorphic effects through T3 receptors (TRs). TRs recruit, in a T3‐dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during development is largely unknown. Here, we analyzed histone modifications at T3 target genes during intestinal metamorphosis, a process that involves de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.
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