RT Journal Article SR Electronic T1 Reconstruction of the global neural crest gene regulatory network in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 508473 DO 10.1101/508473 A1 Ruth M Williams A1 Ivan Candido-Ferreira A1 Emmanouela Repapi A1 Daria Gavriouchkina A1 Upeka Senanayake A1 Jelena Telenius A1 Stephen Taylor A1 Jim Hughes A1 Tatjana Sauka-Spengler YR 2018 UL http://biorxiv.org/content/early/2018/12/30/508473.abstract AB 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.