|ZFIN ID: ZDB-PUB-190322-17|
From Pioneer to Repressor: Bimodal foxd3 Activity Dynamically Remodels Neural Crest Regulatory Landscape In Vivo
Lukoseviciute, M., Gavriouchkina, D., Williams, R.M., Hochgreb-Hagele, T., Senanayake, U., Chong-Morrison, V., Thongjuea, S., Repapi, E., Mead, A., Sauka-Spengler, T.
|Source:||Developmental Cell 47: 608-628.e6 (Journal)|
|Registered Authors:||Sauka-Spengler, Tatjana|
|Keywords:||chromatin dynamics, enhancer, foxd3, gene regulatory network, neural crest, pioneer factor, repressor, stem cells|
|PubMed:||30513303 Full text @ Dev. Cell|
Lukoseviciute, M., Gavriouchkina, D., Williams, R.M., Hochgreb-Hagele, T., Senanayake, U., Chong-Morrison, V., Thongjuea, S., Repapi, E., Mead, A., Sauka-Spengler, T. (2018) From Pioneer to Repressor: Bimodal foxd3 Activity Dynamically Remodels Neural Crest Regulatory Landscape In Vivo. Developmental Cell. 47:608-628.e6.
ABSTRACTThe neural crest (NC) is a transient embryonic stem cell-like population characterized by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant 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 gradually switches from an activator to its well-described role as a transcriptional repressor and potentially uses differential partners for each role. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from "permissive" to "repressive" nucleosome and chromatin organization to maintain multipotency and define cell fates.