Pioneer and repressive functions of p63 during zebrafish embryonic ectoderm specification

• Published in: Nature communications Vol. 10; no. 1; pp. 3049 - 13
• Main Authors: Santos-Pereira, José M, Gallardo-Fuentes, Lourdes, Neto, Ana, Acemel, Rafael D, Tena, Juan J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.07.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Animals, Genetically Modified; Binding; Cell Differentiation - genetics; Cell fate; Chromatin; Chromatin - metabolism; CRISPR-Cas Systems - genetics; Danio rerio; Developmental stages; Down-Regulation; Ectoderm; Ectoderm - embryology; Ectoderm - metabolism; Embryo, Nonmammalian; Embryonic Development - genetics; Embryos; Enhancer Elements, Genetic - genetics; Enhancers; Epidermis - embryology; Epidermis - metabolism; Gene expression; Gene Expression Regulation, Developmental; Gene Knockout Techniques; Models, Animal; Mutants; Neural plate; Neural Plate - embryology; Neural Plate - metabolism; Phenotypes; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Binding - genetics; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Specifications; Trans-Activators - genetics; Trans-Activators - metabolism; Vertebrates; Zebrafish; Zebrafish - embryology; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11121-z

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.