Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/27222
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Genome-Wide Profiling of p63 DNA–Binding Sites Identifies an Element that Regulates Gene Expression during Limb Development in the 7q21 SHFM1 Locus

AuthorsTena, Juan J. CSIC ORCID; Alonso, M. Eva; Calle-Mustienes, Elisa de la CSIC ORCID; Manzanares, Miguel; Gómez-Skarmeta, José Luis CSIC ORCID ; Bokhoven, Hans van; Zhou, Huiqing
Issue DateAug-2010
PublisherPublic Library of Science
CitationPLoS Genetics 6(8): e1001065 (2010)
AbstractHeterozygous mutations in p63 are associated with split hand/foot malformations (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the p63 gene network that includes target genes and regulatory elements may reveal new genes for other malformation disorders. We performed genome-wide DNA–binding profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing (ChIP–seq) in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63. We show that p63 binds to an enhancer element in the SHFM1 locus on chromosome 7q and that this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development. A unique micro-deletion including this enhancer element, but not the DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly indicates disruption of a non-coding cis-regulatory element located more than 250 kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes.
Description15 páginas, 5 figuras, 3 tablas.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pgen.1001065
URIhttp://hdl.handle.net/10261/27222
DOI10.1371/journal.pgen.1001065
ISSN1553-7390
E-ISSN1553-7404
Appears in Collections:(CABD) Artículos

Files in This Item:
File Description SizeFormat
journal.pgen.1001065[1].pdf2,78 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

PubMed Central
Citations

102
checked on May 26, 2022

SCOPUSTM   
Citations

141
checked on May 22, 2022

WEB OF SCIENCETM
Citations

138
checked on May 24, 2022

Page view(s)

350
checked on May 26, 2022

Download(s)

86
checked on May 26, 2022

Google ScholarTM

Check

Altmetric

Dimensions


Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.