Histone variant dictates fate biasing of neural crest cells to melanocyte lineage.
Development
; 147(5)2020 03 12.
Article
em En
| MEDLINE
| ID: mdl-32098766
ABSTRACT
In the neural crest lineage, progressive fate restriction and stem cell assignment are crucial for both development and regeneration. Whereas fate commitment events have distinct transcriptional footprints, fate biasing is often transitory and metastable, and is thought to be moulded by epigenetic programmes. Therefore, the molecular basis of specification is difficult to define. In this study, we established a role for a histone variant, H2a.z.2, in specification of the melanocyte lineage from multipotent neural crest cells. H2a.z.2 silencing reduces the number of melanocyte precursors in developing zebrafish embryos and from mouse embryonic stem cells in vitro We demonstrate that this histone variant occupies nucleosomes in the promoter of the key melanocyte determinant mitf, and enhances its induction. CRISPR/Cas9-based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby, our study establishes the role of a histone variant upstream of the core gene regulatory network in the neural crest lineage. This epigenetic mark is a key determinant of cell fate and facilitates gene activation by external instructive signals, thereby establishing melanocyte fate identity.
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Base de dados:
MEDLINE
Assunto principal:
Histonas
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Proteínas de Peixe-Zebra
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Fator de Transcrição Associado à Microftalmia
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Células-Tronco Embrionárias
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Melanócitos
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Crista Neural
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article