Reconstruction of the Global Neural Crest Gene Regulatory Network In Vivo

• DOI: 10.1016/j.devcel.2019.10.003
• Publication Date: 2019-10-21T15:20:03Z
• Authors: Ruth M. Williams; Ivan Candido-Ferr...; Emmanouela Repapi; Daria Gavriouchkina; Upeka Senanayake; Irving T.C. Ling; Jelena Telenius; Stephen Taylor; Jim Hughes; Tatjana Sauka-Spe...
• Keywords: Gene regulatory network

Highlights•Profiling chromatin dynamics uncovers complete repertoire of neural crest (NC) enhancers•NC super-enhancers act additively to sustain network robustness•Enhancer clustering reveals early split between neural-NC and canonical NC programs•Global construction cranial gene regulatory networkSummaryPrecise control developmental processes is encoded in the genome form networks (GRNs). Such multi-factorial systems are difficult decode vertebrates owing their complex hierarchies dynamic molecular interactions. Here we present a genome-wide vivo reconstruction GRN underlying development multipotent embryonic cell population. By coupling NC-specific epigenomic transcriptional profiling at population single-cell levels with genome/epigenome engineering vivo, identify multiple layers governing ontogeny, including enhancers super-enhancers, novel trans-factors, cis-signatures allowing reverse NC-GRN unprecedented resolution. Furthermore, identification dissection divergent upstream combinatorial codes has afforded new insights into opposing circuits that define fates during ontogeny. Our integrated approach, cell-type-specific broad implications for discovery investigation.Graphical abstract