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Closed Access item Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes

Authors:Martín, David
Pantoja, Cristina
Fernández-Miñán, Ana
Valdes-Quezada, Christian
Moltó, Eduardo
Matesanz, F.
Bogdanovic, Ozren
Calle-Mustienes, Elisa de la
Domínguez, Orlando
Taher, Leila
Furlan-Magaril, Mayra
Alcina, Antonio
Cañón, Susana
Fedetz, María
Blasco Marhuenda, María Antonia
Pereira, Paulo S.
Ovcharenko, Ivan
Recillas-Targa, Félix
Montoliu, Lluís
Manzanares, Miguel
Guigó, Roderic
Serrano, Manuel
Casares, Fernando
Gómez-Skarmeta, José Luis
Keywords:DNA-binding proteins, Genome, Multiple sclerosis, Nuclear protein, Polymorphism, Transcription factors
Issue Date:22-May-2011
Publisher:Nature Publishing Group
Citation:Nature Structural and Molecular Biology 18(6): 708-714 (2011)
Abstract:Many genomic alterations associated with human diseases localize in noncoding regulatory elements located far from the promoters they regulate, making it challenging to link noncoding mutations or risk-associated variants with target genes. The range of action of a given set of enhancers is thought to be defined by insulator elements bound by the 11 11 11 11 zinc-finger nuclear factor CCCTC-binding protein (CTCF). Here we analyzed the genomic distribution of CTCF in various human, mouse and chicken cell types, demonstrating the existence of evolutionarily conserved CTCF-bound sites beyond mammals. These sites preferentially flank transcription factor–encoding genes, often associated with human diseases, and function as enhancer blockers in vivo, suggesting that they act as evolutionarily invariant gene boundaries. We then applied this concept to predict and functionally demonstrate that the polymorphic variants associated with multiple sclerosis located within the EVI5 gene impinge on the adjacent gene GFI1.
Description:7 páginas, 6 figuras, 1 tabla.
Publisher version (URL):http://dx.doi.org/10.1038/nsmb.2059
E-ISSNmetadata.dc.identifier.doi = DOI:1545-9985
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