English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/127907
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding

AuthorsCalle-Mustienes, Elisa de la ; Giráldez-Pérez, Rosa María; Carvajal, Jaime J. ; Gómez-Skarmeta, José Luis ; Tomlinson, Ian
Issue Date21-Aug-2014
PublisherElsevier
CitationCell Reports 8(4): 983-990 (2014)
AbstractA rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes aMendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ~20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences inGREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in ApcMin mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors. © 2014 The Authors.
DescriptionUnder a Creative Commons license.-- et al.
Publisher version (URL)http://dx.doi.org/10.1016/j.celrep.2014.07.020
URIhttp://hdl.handle.net/10261/127907
DOI10.1016/j.celrep.2014.07.020
Identifiersissn: 2211-1247
Appears in Collections:(CABD) Artículos
Files in This Item:
File Description SizeFormat 
polymorphic_enhancer_Lewis.pdf233,24 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


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