Pioneer and repressive functions of p63 during zebrafish embryonic ectoderm specification.
Nat Commun
; 10(1): 3049, 2019 07 11.
Article
em En
| MEDLINE
| ID: mdl-31296872
ABSTRACT
The transcription factor p63 is a master regulator of ectoderm development. Although previous studies show that p63 triggers epidermal differentiation in vitro, the roles of p63 in developing embryos remain poorly understood. Here, we use zebrafish embryos to analyze in vivo how p63 regulates gene expression during development. We generate tp63-knock-out mutants that recapitulate human phenotypes and show down-regulated epidermal gene expression. Following p63-binding dynamics, we find two distinct functions clearly separated in space and time. During early development, p63 binds enhancers associated to neural genes, limiting Sox3 binding and reducing neural gene expression. Indeed, we show that p63 and Sox3 are co-expressed in the neural plate border. On the other hand, p63 acts as a pioneer factor by binding non-accessible chromatin at epidermal enhancers, promoting their opening and epidermal gene expression in later developmental stages. Therefore, our results suggest that p63 regulates cell fate decisions during vertebrate ectoderm specification.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Transativadores
/
Regulação da Expressão Gênica no Desenvolvimento
/
Proteínas de Peixe-Zebra
/
Desenvolvimento Embrionário
/
Ectoderma
/
Placa Neural
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article