Abstract
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.
Highlights
Thyroid hormones (TH) and Glucocorticoids (GC) are ubiquitous mediators of endocrine signalling systems coordinating homeostasis, a response to environmental challenges and development throughout life, starting from early development until death.These systems are highly conserved in vertebrates [1,2,3], where they regulate similar processes across taxa ranging from fish to amphibians to birds and mammals [4]
We demonstrate that the action of TH and GC is not limited to the simple addition of the effects of TH and GC, and that the known action of GC on dio2/dio3 cannot explain the diversity of transcriptional responses in tailfin
The detection of Differentially Methylated Regions (DMRs) is based on non-parametric permutation tests aimed at finding the maximal width and peak height obtained when comparing two profiles without biological contrast. This defines the thresholds of biological and technological noise above which peaks correspond to actual DMRs, with their width and height corresponding to the genome span of the DMR, and the amplitude of DNA methylation changes, respectively
Summary
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. 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 nonnegligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. 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.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
