GSE68087
Active DNA demethylation at enhancers during the vertebrate phylotypic period
The vertebrate body plan and organs are shaped during a conserved embryonic phase called the phylotypic stage, however the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of enhancers during the phylotypic period in zebrafish, Xenopus and mouse. These enhancers are linked to developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Binding of Tet proteins to (hydroxy)methylated DNA, and enrichment of hydroxymethylcytosine on these regions, implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1/2/3 in zebrafish caused reduced chromatin accessibility and increased methylation levels specifically on these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study reveals a novel regulatory module associated with the most conserved phase of vertebrate embryogenesis and uncovers an ancient developmental role for the Tet dioxygenases. Overall design: MethylC-Seq in zebrafish embryos, MethylC-seq in Xenopus tropicalis embryos, MethylC-seq in mouse embryos, MethylC-seq in zebrafish tissues, MethylC-seq in Xenopus tropicalis tissues, TAB-seq in zebrafish embryos, TAB-seq in Xenopus tropicalis embryos, TAB-seq in mouse embryos, RNA-seq in zebrafish embryos, RNA-seq in mouse embryos