Pioneer and Repressive Functions of P63 During Zebrafish Embryonic Ectoderm Specification
Overview
Affiliations
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.
p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer.
Sadu Murari L, Kunkel S, Shetty A, Bents A, Bhandary A, Rivera-Mulia J Cells. 2025; 14(1.
PMID: 39791744 PMC: 11719615. DOI: 10.3390/cells14010043.
Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.
Baniulyte G, McCann A, Woodstock D, Sammons M Nucleic Acids Res. 2024; 52(22):13812-13831.
PMID: 39565223 PMC: 11662943. DOI: 10.1093/nar/gkae1143.
Hemichordate cis-regulatory genomics and the gene expression dynamics of deuterostomes.
Perez-Posada A, Lin C, Fan T, Lin C, Chen Y, Gomez-Skarmeta J Nat Ecol Evol. 2024; 8(12):2213-2227.
PMID: 39424956 PMC: 11618098. DOI: 10.1038/s41559-024-02562-x.
Hypoxia-induced immortalization of primary cells depends on Tfcp2L1 expression.
Otero-Albiol D, Santos-Pereira J, Lucena-Cacace A, Clemente-Gonzalez C, Munoz-Galvan S, Yoshida Y Cell Death Dis. 2024; 15(2):177.
PMID: 38418821 PMC: 10902313. DOI: 10.1038/s41419-024-06567-z.
Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.
Munoz-Galvan S, Verdugo-Sivianes E, Santos-Pereira J, Estevez-Garcia P, Carnero A J Exp Clin Cancer Res. 2024; 43(1):57.
PMID: 38403587 PMC: 10895852. DOI: 10.1186/s13046-024-02988-y.