Here we provide additional information such as scripts and applications to access data generated in the FoxD3 Project.
The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. We have performed NC-specific transcriptional and epigenomic profiling of foxd3-mutant versus wild type cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3-expressing premigratory NC, our analysis shows that during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis-regulatory elements and reshuffling nucleosomes. Strikingly, foxd3 then switches from an activator to its canonical role as a transcriptional repressor. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from permissive to repressive nucleosome/chromatin organisation to maintain stemness and define cell fates.
neural crest, enhancer, pioneer factor, gene regulatory network, stem cells
Danio rerio
From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo
Martyna Lukoseviciute*1, Daria Gavriouchkina*1,4, Ruth M Williams*1, Tatiana Hochgreb-Hagele1, Upeka Senanayake1, Vanessa Chong-Morrison1, Supat Thongjuea2, Emmanouela Repapi3, Adam Mead2, Tatjana Sauka-Spengler1
* co-first authors
Corresponding author: Tatjana Sauka-Spengler (tatjana.sauka-spengler@imm.ox.ac.uk)
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University of Oxford,
MRC Weatherall Institute of Molecular Medicine,
Radcliffe Department of Medicine,
Oxford, OX3 9DS, UK -
University of Oxford,
MRC Weatherall Institute of Molecular Medicine,
Molecular Haematology Unit,
Oxford, OX3 9DS, UK -
University of Oxford,
MRC WIMM Centre for Computational Biology,
MRC Weatherall Institute of Molecular Medicine,
Oxford, OX3 9DS, UK -
Present address:
Okinawa Institute of Science and Technology,
Molecular Genetics Unit,
Onna, 904-0495 Japan
Martyna Lukoseviciute, Daria Gavriouchkina, Ruth M Williams, Tatiana Hochgreb-Hagele, Upeka Senanayake, Vanessa Chong-Morrison, Tatjana Sauka-Spengler: Sauka-Spengler lab based at Weatherall Institute of Molecular Medicine and at Radcliffe Department of Medicine, University of Oxford
Adam Mead: Mead lab based at Weatherall Institute of Molecular Medicine, University of Oxford
Emmanouela Repapi is part of Computational Biology Research Group and Supat Thongjuea is part of the MRC WIMM Centre for Computational Biology
This work was supported by MRC (G0902418), Lister Institute prize, Leverhulme Trust grant (RPG-2015-592026), March of Dimes Basil OConnor Award to Tatjana Sauka-Spengler, and SNF Fellowship to Daria Gavriouchkina.