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Reconstruction of the global neural crest gene regulatory network in vivo

View ORCID ProfileRuth M Williams, View ORCID ProfileIvan Candido-Ferreira, Emmanouela Repapi, View ORCID ProfileDaria Gavriouchkina, Upeka Senanayake, View ORCID ProfileJelena Telenius, View ORCID ProfileStephen Taylor, View ORCID ProfileJim Hughes, View ORCID ProfileTatjana Sauka-Spengler
doi: https://doi.org/10.1101/508473
Ruth M Williams
1University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK
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  • ORCID record for Ruth M Williams
Ivan Candido-Ferreira
1University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK
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Emmanouela Repapi
2University of Oxford, MRC Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
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Daria Gavriouchkina
1University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK
4Okinawa Institute of Science and Technology, Molecular Genetics Unit, Onna, 904-0495, Japan
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Upeka Senanayake
1University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK
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Jelena Telenius
2University of Oxford, MRC Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
3University of Oxford, MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
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Stephen Taylor
2University of Oxford, MRC Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
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Jim Hughes
2University of Oxford, MRC Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
3University of Oxford, MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK
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Tatjana Sauka-Spengler
1University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK
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  • ORCID record for Tatjana Sauka-Spengler
  • For correspondence: tatjana.sauka-spengler@imm.ox.ac.uk
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Abstract

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.

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Posted December 30, 2018.
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Reconstruction of the global neural crest gene regulatory network in vivo
Ruth M Williams, Ivan Candido-Ferreira, Emmanouela Repapi, Daria Gavriouchkina, Upeka Senanayake, Jelena Telenius, Stephen Taylor, Jim Hughes, Tatjana Sauka-Spengler
bioRxiv 508473; doi: https://doi.org/10.1101/508473
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Reconstruction of the global neural crest gene regulatory network in vivo
Ruth M Williams, Ivan Candido-Ferreira, Emmanouela Repapi, Daria Gavriouchkina, Upeka Senanayake, Jelena Telenius, Stephen Taylor, Jim Hughes, Tatjana Sauka-Spengler
bioRxiv 508473; doi: https://doi.org/10.1101/508473

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