SAT-551 Thyroid Hormone Effects on the Methylome During Post-Embryonic Development

Abstract

Thyroid hormones (TH) have been shown to govern post-embryonic development in vertebrates inducing multiples effects. Recently, TH were shown to regulate the expression of genes coding for DNA methylation modifying enzymes. Acting on DNA methylation is an important means of regulating the expression of gene clusters and a central mechanism for coordinating developmental transitions. However, DNA methylation is dynamic and also integrate signals from the constantly changing environment. Certain variation of DNA methylation at these developmental transitions can confer on the genome a risk situation that can have lifelong consequences (cardiovascular and metabolism diseases, cancer or nervous system associated illness). Our objective is to locate TH induced variation of DNA methylation profiles to characterize potential determinants for certain pathologies and / or adaptation to a variation of the environment. We have thus initiated the mapping of DNA methylation following treatment with T3, using a method for capturing methylated DNA (MethylCap) combined with high-throughput sequencing (MethylCap-Seq). Magnetic beads allow for capture and fractionation of methylated DNA by CpG density. Here, we will focus on the highly methylated fraction of DNA. Our model of developmental transition is the amphibian metamorphosis, a post-embryonic process regulated by TH. Additionally, stress during metamorphosis might also induce potential phenotype propagation to adult forms, highlighting its importance in driving adaptation to fluctuating environments. We have compared TH induced methylation profiles in the hind limb and caudal epidermal, two organs with contrasted fate during metamorphosis (respectively morphogenesis and cell death). The results shown that TH affect the methylome with a strong tendency for DNA methylation marks to be removed. The majority of differential methylated regions (DMR) are tissue specific. However, few DMRs are found in both tissues and show either identical or opposite variations. The DMRs are generally not localize near genes regulated or not by the hormones. In conclusion, at post-embryonic transition in amphibians, TH induce mainly tissues-specific DNA demethylation not directly related to gene transcription.