Organ-specific effects on target binding due to knockout of thyroid hormone receptor alpha during Xenopus metamorphosis

Thyroid hormone (T3) is essential for normal development and metabolism, especially during postembryonic development, a period around birth in mammals when plasma T3 levels reach their peak. T3 functions through two T3 receptors, TR alpha and TR beta. However, little is known about the tissue-specific functions of TRs during postembryonic development because of maternal influence and difficulty in manipulation of mammalian models. We have studied Xenopus tropicalis metamorphosis as a model for human postembryonic development. By using TR alpha knockout (Xtr center dot thra(tmshi)) tadpoles, we have previously shown that TR alpha is important for T3-dependent intestinal remodeling and hindlimb development but not tail resorption during metamorphosis. Here, we have identified genes bound by TR in premetamorphic wild-type and Xtr center dot thra(tmshi) tails with or without T3 treatment by using chromatin immunoprecipitation-sequencing and compared them with those in the intestine and hindlimb. Compared to other organs, the tail has much fewer genes bound by TR or affected by TR alpha knockout. Bioinformatic analyses revealed that among the genes bound by TR in wild-type but not Xtr center dot thra(tmshi) organs, fewer gene ontology (GO) terms or biological pathways related to metamorphosis were enriched in the tail compared to those in the intestine and hindlimb. This difference likely underlies the drastic effects of TR alpha knockout on the metamorphosis of the intestine and hindlimb but not the tail. Thus, TR alpha has tissue-specific roles in regulating T3-dependent anuran metamorphosis by directly targeting the pathways and GO terms important for metamorphosis.