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The neural crest (NC) is a transient embryonic stem cell populations 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 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.

Original publication

DOI

10.1101/213611

Type

Journal article

Journal

Developmental Cell

Publisher

Elsevier

Publication Date

03/12/2018