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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Format: | Article |
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Frontiers Media S.A.
2020-04-01
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Series: | Frontiers in Genetics |
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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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institution | Directory Open Access Journal |
issn | 1664-8021 |
language | English |
last_indexed | 2024-12-10T08:51:36Z |
publishDate | 2020-04-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Genetics |
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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