GSE138905
ATAC-seq identifies accessible chromatin domains in gastrula stage Xenopus laevis
In the embryo, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner, and the mechanisms for the loss of responsiveness are not well understood. To test the hypothesis that loss of competence is associated with changes in chromatin accessibility, we adapted the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) for use in Xenopus laevis to evaluate genome-wide changes in chromatin accessibility in early and late gastrula stages. ATAC-seq was performed on presumptive ectoderm (animal caps) explanted at the blastula stage and cultured until siblings reached early (stage 10) or late (stage 12) gastrula stage. Approximately 70,000 accessible regions were identified at intergenic regions, introns, promoters, and transcription termination sites at both stages. Accessibility decreased from stage 10 to stage 12 at 279 promoters, including developmental regulators such as Foxh1, chordin, and VegT. Accessible chromatin domains overlap extensively with previously reported p300 binding sites, consistent with putative cis-regulatory modules (pCRMs), and these pCRMs are enriched for binding motifs for pluripotency factors, including Sox, Oct/Pou, and KLF binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence, but inhibition of histone deacetylases increases acetylation at these promoters and extends competence for dorsal gene induction by Wnt signaling. In contrast, the promoters for genes involved in mesoderm and neural crest development remain open through gastrulation, and histone deacetylase inhibition does not extend competence for mesoderm or neural crest induction. These data suggest that chromatin state regulates the loss of competence to inductive signals in a context-dependent manner. Overall design: ATAC-seq performed on ectodermal explants from stage 10 (early gastrula) and stage 12 (late gastrula).