TY - JOUR T1 - Reconstruction of the global neural crest gene regulatory network <em>in vivo</em> JF - bioRxiv DO - 10.1101/508473 SP - 508473 AU - Ruth M Williams AU - Ivan Candido-Ferreira AU - Emmanouela Repapi AU - Daria Gavriouchkina AU - Upeka Senanayake AU - Jelena Telenius AU - Stephen Taylor AU - Jim Hughes AU - Tatjana Sauka-Spengler Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/12/30/508473.abstract N2 - Precise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and transient dynamic molecular interactions. Here we present a genome-wide in vivo reconstruction of the GRN underlying development of neural crest (NC), an emblematic embryonic multipotent cell population. By coupling NC-specific epigenomic and single-cell transcriptome profiling with genome/epigenome engineering in vivo, we identify multiple regulatory layers governing NC ontogeny, including NC-specific enhancers and super-enhancers, novel trans-factors and cis-signatures. Assembling the NC regulome has allowed the comprehensive reverse engineering of the NC-GRN at unprecedented resolution. Furthermore, identification and dissection of divergent upstream combinatorial regulatory codes has afforded new insights into opposing gene circuits that define canonical and neural NC fates. Our integrated approach, allowing dissection of cell-type-specific regulatory circuits in vivo, has broad implications for GRN discovery and investigation. ER -