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Thyroid hormone (T3) affects development and metabolism in vertebrates. We have been studying intestinal remodeling during T3-dependent  Xenopus  metamorphosis as a model for organ maturation and formation of adult organ-specific stem cells during vertebrate postembryonic development, a period characterized by high levels of plasma T3. T3 is believed to affect development by regulating target gene transcription through T3 receptors (TRs). While many T3 response genes have been identified in different animal species, few have been shown to be direct target genes  in vivo , especially during development. Here we generated a set of genomic microarray chips covering about 8000 bp flanking the predicted transcription start sites in  Xenopus tropicalis  for genome wide identification of TR binding sites. By using the intestine of premetamorphic tadpoles treated with or without T3 and for chromatin immunoprecipitation assays with these chips, we determined the genome-wide binding of TR in the control and T3-treated tadpole intestine. We further validated TR binding  in vivo  and analyzed the regulation of selected genes. We thus identified 278 candidate direct TR target genes. We further provided evidence that these genes are regulated by T3 and likely involved in the T3-induced formation of adult intestinal stem cells during metamorphosis.

Genome-wide identification of thyroid hormone receptor targets in the remodeling intestine during Xenopus tropicalis metamorphosis