RT Journal Article SR Electronic T1 From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 213611 DO 10.1101/213611 A1 Gavriouchkina, Daria A1 Williams, Ruth M A1 Lukoseviciute, Martyna A1 Hochgreb-Hägele, Tatiana A1 Senanayake, Upeka A1 Chong-Morrison, Vanessa A1 Thongjuea, Supat A1 Repapi, Emmanouela A1 Mead, Adam A1 Sauka-Spengler, Tatjana YR 2017 UL http://biorxiv.org/content/early/2017/11/22/213611.abstract AB The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform 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 reshuffing 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.