PUBLICATION
From Pioneer to Repressor: Bimodal foxd3 Activity Dynamically Remodels Neural Crest Regulatory Landscape In Vivo
- Authors
- Lukoseviciute, M., Gavriouchkina, D., Williams, R.M., Hochgreb-Hagele, T., Senanayake, U., Chong-Morrison, V., Thongjuea, S., Repapi, E., Mead, A., Sauka-Spengler, T.
- ID
- ZDB-PUB-190322-17
- Date
- 2018
- 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
- Datasets
- GEO:GSE106676
- MeSH Terms
-
- Animals
- Chromatin Assembly and Disassembly
- Enhancer Elements, Genetic
- Forkhead Transcription Factors/genetics
- Forkhead Transcription Factors/metabolism*
- Gene Expression Regulation, Developmental*
- Neural Crest/embryology
- Neural Crest/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30513303 Full text @ Dev. Cell
Citation
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.
Abstract
The 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping