Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish.

Autor: Jang HS; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.; Present address: Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA., Chen Y; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Ge J; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Wilkening AN; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Hou Y; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Lee HJ; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Choi YR; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Lowdon RF; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Xing X; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Li D; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Kaufman CK; Department of Medicine, Division of Medical Oncology, and Department of Developmental Biology, Washington University in Saint Louis, St. Louis, MO, USA., Johnson SL; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA., Wang T; Department of Genetics, Washington University School of Medicine, St Louis, MO, USA. twang@wustl.edu.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. twang@wustl.edu.; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. twang@wustl.edu.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2021 Oct 04; Vol. 22 (1), pp. 282. Date of Electronic Publication: 2021 Oct 04.
DOI: 10.1186/s13059-021-02493-x
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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