PT  - JOURNAL ARTICLE
AU  - Gavriouchkina, Daria
AU  - Williams, Ruth M
AU  - Lukoseviciute, Martyna
AU  - Hochgreb-Hägele, Tatiana
AU  - Senanayake, Upeka
AU  - Chong-Morrison, Vanessa
AU  - Thongjuea, Supat
AU  - Repapi, Emmanouela
AU  - Mead, Adam
AU  - Sauka-Spengler, Tatjana
TI  - From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape <em>in vivo</em>
AID  - 10.1101/213611
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 213611
4099  - http://biorxiv.org/content/early/2017/11/22/213611.short
4100  - http://biorxiv.org/content/early/2017/11/22/213611.full
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.