Transcriptome and Methylome Analysis Reveal Complex Cross-Talks between Thyroid Hormone and Glucocorticoid Signaling...

Area of Science:

• Endocrinology
• Developmental Biology
• Genomics

Background:

• Most endocrinology research focuses on single hormones, neglecting interactions between hormone signaling pathways.
• Thyroid hormone (TH) and glucocorticoid (GC) signaling are crucial for vertebrate development, particularly metamorphosis.
• The cross-talk between TH and GC signaling during Xenopus tropicalis metamorphosis remains poorly understood.

Purpose of the Study:

• To characterize the complex interactions between thyroid hormone and glucocorticoid signaling pathways.
• To investigate genome-wide gene expression and DNA methylation changes in response to TH and GC.
• To model biological networks and understand the nature of hormonal cross-talks during metamorphosis.

Main Methods:

• Utilized functional genomics in Xenopus tropicalis tailfin tissue, a highly responsive model.
• Generated genome-wide DNA methylation profiles and measured gene expression changes after hormonal treatments.
• Employed data clustering to identify distinct biological responses and system biology for network modeling.

Main Results:

• Gene expression is primarily regulated by individual hormones (T3 or CORT) or their additive effects.
• A significant fraction of genes (12%) exhibited complex, non-additive regulatory patterns, indicating intricate signaling interactions.
• DNA methylation changes were predominantly driven by cross-talks between TH and GC, showing an inverse relationship to gene expression regulation.

Conclusions:

• Cross-talks between TH and GC signaling are more complex than previously assumed, often resulting in synergistic effects (TH ∙ GC > TH + GC).
• DNA methylation dynamics are highly responsive to hormonal cross-talks and appear buffered from direct gene expression changes.
• These findings reveal a sophisticated interplay between hormonal signaling and epigenetic regulation during development.