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Cells January 1, 2021; 10 (9):
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Transcriptome and Methylome Analysis Reveal Complex Cross-Talks between Thyroid Hormone and Glucocorticoid Signaling at Xenopus Metamorphosis.

Buisine N , Grimaldi A , Jonchere V , Rigolet M , Blugeon C , Hamroune J , Sachs LM .

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.

PubMed ID: 34572025
PMC ID: PMC8468809
Article link: Cells
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: agr2 ctrl dnmt1 ezh2 mecp2 smarca4 uhrf1 usp7
GO keywords: thyroid hormone mediated signaling pathway [+]

Article Images: [+] show captions