Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish.
Animals
Cell Differentiation
/ genetics
Chromatin
/ metabolism
Chromatophores
/ metabolism
CpG Islands
DNA Methylation
Epigenesis, Genetic
Gene Regulatory Networks
Melanophores
/ metabolism
Neural Crest
/ cytology
Regulatory Sequences, Nucleic Acid
Transcription Factors
/ metabolism
Transcription, Genetic
Zebrafish
/ genetics
Zebrafish Proteins
/ metabolism
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
04 10 2021
04 10 2021
Historique:
received:
26
03
2021
accepted:
09
09
2021
entrez:
5
10
2021
pubmed:
6
10
2021
medline:
29
1
2022
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34607603
doi: 10.1186/s13059-021-02493-x
pii: 10.1186/s13059-021-02493-x
pmc: PMC8489059
doi:
Substances chimiques
Chromatin
0
Transcription Factors
0
Zebrafish Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
282Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007067
Pays : United States
Organisme : NIEHS NIH HHS
ID : U24 ES026699
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG007175
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009391
Pays : United States
Informations de copyright
© 2021. The Author(s).
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