XB-ART-56750Dev Biol June 1, 2020; 462 (1): 20-35.
Chromatin accessibility and histone acetylation in the regulation of competence in early development.
As development proceeds, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner. While key inductive signaling pathways within competent cells are well-described at a molecular level, the mechanisms by which tissues lose responsiveness to inductive signals are not well understood. Localized activation of Wnt signaling before zygotic gene activation in Xenopus laevis leads to dorsal development, but competence to induce dorsal genes in response to Wnts is lost by the late blastula stage. We hypothesize that loss of competence is mediated by changes in histone modifications leading to a loss of chromatin accessibility at the promoters of Wnt target genes. We use ATAC-seq to evaluate genome-wide changes in chromatin accessibility across several developmental stages. Based on overlap with p300 binding, we identify thousands of putative cis-regulatory elements at the gastrula stage, including sites that lose accessibility by the end of gastrulation and are enriched for pluripotency factor binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence in the early gastrula while genes involved in mesoderm and neural crest development maintain accessibility at their promoters. Inhibition of histone deacetylases increases acetylation at the promoters of dorsal Wnt target genes and extends competence for dorsal gene induction by Wnt signaling. Histone deacetylase inhibition, however, is not sufficient to 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.
PubMed ID: 32119833
PMC ID: PMC7225061
Article link: Dev Biol
Genes referenced: 1a11 axin2 barhl2 cdx2 chrd.1 crebbp gsc hoxa1 hoxd1 jarid2 lefty myod1 nodal3.1 pax3 pou3f2 pou5f3.1 pou5f3.2 pou5f3.3 sia1 sia2 snai1 snai2 tbxt tcf3 twist1 vegt wnt5b wnt8a
Antibodies: H3f3a Ab24 H3f3a Ab26 H3f3a Ab39 IgG Ab1
GEO Series: GSE138905: Xenbase, NCBI