Functional Conservation of Divergent p63-Bound cis-Regulatory Elements

The transcription factor p63 is an essential regulator of vertebrate ectoderm development, including epidermis, limbs, and craniofacial tissues. Here, we have investigated the evolutionary conservation of p63 binding sites (BSs) between zebrafish and human. First, we have analyzed sequence conservat...

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Main Authors: Lourdes Gallardo-Fuentes, José M. Santos-Pereira, Juan J. Tena
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-04-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.00339/full
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author Lourdes Gallardo-Fuentes
José M. Santos-Pereira
Juan J. Tena
author_facet Lourdes Gallardo-Fuentes
José M. Santos-Pereira
Juan J. Tena
author_sort Lourdes Gallardo-Fuentes
collection DOAJ
description The transcription factor p63 is an essential regulator of vertebrate ectoderm development, including epidermis, limbs, and craniofacial tissues. Here, we have investigated the evolutionary conservation of p63 binding sites (BSs) between zebrafish and human. First, we have analyzed sequence conservation of p63 BSs by comparing ChIP-seq data from human keratinocytes and zebrafish embryos, observing a very poor conservation. Next, we compared the gene regulatory network orchestrated by p63 in both species and found a high overlap between them, suggesting a high degree of functional conservation during evolution despite sequence divergence and the large evolutionary distance. Finally, we used transgenic reporter assays in zebrafish embryos to functionally validate a set of equivalent p63 BSs from zebrafish and human located close to genes involved in epidermal development. Reporter expression was driven by human and zebrafish BSs to many common tissues related to p63 expression domains. Therefore, we conclude that the gene regulatory network controlled by p63 is highly conserved across vertebrates despite the fact that p63-bound regulatory elements show high divergence.
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spelling doaj.art-46c41cfbbbc7405180349872f5c93fd72022-12-22T01:55:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-04-011110.3389/fgene.2020.00339522426Functional Conservation of Divergent p63-Bound cis-Regulatory ElementsLourdes Gallardo-FuentesJosé M. Santos-PereiraJuan J. TenaThe transcription factor p63 is an essential regulator of vertebrate ectoderm development, including epidermis, limbs, and craniofacial tissues. Here, we have investigated the evolutionary conservation of p63 binding sites (BSs) between zebrafish and human. First, we have analyzed sequence conservation of p63 BSs by comparing ChIP-seq data from human keratinocytes and zebrafish embryos, observing a very poor conservation. Next, we compared the gene regulatory network orchestrated by p63 in both species and found a high overlap between them, suggesting a high degree of functional conservation during evolution despite sequence divergence and the large evolutionary distance. Finally, we used transgenic reporter assays in zebrafish embryos to functionally validate a set of equivalent p63 BSs from zebrafish and human located close to genes involved in epidermal development. Reporter expression was driven by human and zebrafish BSs to many common tissues related to p63 expression domains. Therefore, we conclude that the gene regulatory network controlled by p63 is highly conserved across vertebrates despite the fact that p63-bound regulatory elements show high divergence.https://www.frontiersin.org/article/10.3389/fgene.2020.00339/fullp63transcription factor binding sitesfunctional conservationsequence divergencehumanzebrafish
spellingShingle Lourdes Gallardo-Fuentes
José M. Santos-Pereira
Juan J. Tena
Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
Frontiers in Genetics
p63
transcription factor binding sites
functional conservation
sequence divergence
human
zebrafish
title Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
title_full Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
title_fullStr Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
title_full_unstemmed Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
title_short Functional Conservation of Divergent p63-Bound cis-Regulatory Elements
title_sort functional conservation of divergent p63 bound cis regulatory elements
topic p63
transcription factor binding sites
functional conservation
sequence divergence
human
zebrafish
url https://www.frontiersin.org/article/10.3389/fgene.2020.00339/full
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