Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish
- Jang, H.S., Chen, Y., Ge, J., Wilkening, A.N., Hou, Y., Lee, H.J., Choi, Y.R., Lowdon, R.F., Xing, X., Li, D., Kaufman, C.K., Johnson, S.L., Wang, T.
- Genome biology 22: 282 (Journal)
- Registered Authors
- Chen, Yujie, Hou, Yiran, Johnson, Stephen L., Lee, Hyung Joo, Wang, Ting
- MeSH Terms
- Cell Differentiation/genetics*
- CpG Islands
- DNA Methylation
- Epigenesis, Genetic*
- Gene Regulatory Networks
- Neural Crest/cytology
- Neural Crest/metabolism
- Regulatory Sequences, Nucleic Acid
- Transcription Factors/metabolism
- Transcription Factors/physiology
- Transcription, Genetic
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology
- 34607603 Full text @ Genome Biol.
Jang, H.S., Chen, Y., Ge, J., Wilkening, A.N., Hou, Y., Lee, H.J., Choi, Y.R., Lowdon, R.F., Xing, X., Li, D., Kaufman, C.K., Johnson, S.L., Wang, T. (2021) Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish. Genome biology. 22:282.
Background Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood.
Results We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a's potential regulatory role in guanine synthesis pathway.
Conclusions Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes