Transcriptome and Methylome Analysis Reveal Complex Cross-Talks between Thyroid Hormone and Glucocorticoid Signaling at Xenopus Metamorphosis

Cells. 2021 Sep 9;10(9):2375. doi: 10.3390/cells10092375.


Background: Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during Xenopus tropicalis metamorphosis.

Methods: We used functional genomics to derive genome wide profiles of methylated DNA and measured changes of gene expression after hormonal treatments of a highly responsive tissue, tailfin. Clustering classified the data into four types of biological responses, and biological networks were modeled by system biology.

Results: We found that gene expression is mostly regulated by either T3 or CORT, or their additive effect when they both regulate the same genes. A small but non-negligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. Strikingly, DNA methylation changes display the opposite and are dominated by cross-talks.

Conclusion: Cross-talks between thyroid hormones and glucocorticoids are more complex than initially envisioned and are not limited to the simple addition of their individual effects, a statement that can be summarized with the pseudo-equation: TH GC > TH + GC. DNA methylation changes are highly dynamic and buffered from genome expression.

Keywords: DNA methylation; Xenopus metamorphosis; cross-talks; functional genomics; glucocorticoids; thyroid hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental / genetics
  • Genome / genetics
  • Glucocorticoids / metabolism*
  • Metamorphosis, Biological / physiology*
  • Signal Transduction / physiology*
  • Thyroid Hormones / metabolism*
  • Transcriptome / genetics*
  • Xenopus / genetics*
  • Xenopus / metabolism*


  • Glucocorticoids
  • Thyroid Hormones