English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/50247
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

Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors

AuthorsDelgado, M. Dolores ; Benhattar, Jean
Issue Date2007
PublisherOxford University Press
CitationNucleic Acids Research 35(21): 7372-7388 (2007)
AbstractBORIS, like other members of the 'cancer/testis antigen' family, is normally expressed in testicular germ cells and repressed in somatic cells, but is aberrantly activated in cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5′-flanking region. Using 5′ RACE, we identified three promoters, designated A, B and C, corresponding to transcription start sites at -1447, -899 and -658 bp upstream of the first ATG. Alternative promoter usage generated at least five alternatively spliced BORIS mRNAs with different half-lives determined by varying 5′-UTRs. In normal testis, BORIS is transcribed from all three promoters, but 84% of the 30 cancer cell lines tested used only promoter(s) A and/or C while the others utilized primarily promoters B and C. The differences in promoter usage between normal and cancer cells suggested that they were subject to differential regulation. We found that DNA methylation and functional p53 contributes to the negative regulation of each promoter. Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS. © 2007 The Author(s).
DescriptionThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkm896
URIhttp://hdl.handle.net/10261/50247
DOI10.1093/nar/gkm896
Identifiersdoi: 10.1093/nar/gkm896
issn: 0305-1048
Appears in Collections:(IBBTEC) Artículos
Files in This Item:
File Description SizeFormat 
CTCF-paralogous.pdf533,79 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.