title: Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes.
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 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.
authors: Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.
authors: David
authors: D
authors: Martin
authors: Cristina
authors: C
authors: Pantoja
authors: Ana
authors: A
authors: Fernández Miñán
authors: Christian
authors: C
authors: Valdes-Quezada
authors: Eduardo
authors: E
authors: Moltó
authors: Fuencisla
authors: F
authors: Matesanz
authors: Ozren
authors: O
authors: Bogdanović
authors: Elisa
authors: E
authors: de la Calle-Mustienes
authors: Orlando
authors: O
authors: Domínguez
authors: Leila
authors: L
authors: Taher
authors: Mayra
authors: M
authors: Furlan-Magaril
authors: Antonio
authors: A
authors: Alcina
authors: Susana
authors: S
authors: Cañón
authors: María
authors: M
authors: Fedetz
authors: María A
authors: MA
authors: Blasco
authors: Paulo S
authors: PS
authors: Pereira
authors: Ivan
authors: I
authors: Ovcharenko
authors: Félix
authors: F
authors: Recillas-Targa
authors: Lluís
authors: L
authors: Montoliu
authors: Miguel
authors: M
authors: Manzanares
authors: Roderic
authors: R
authors: Guigó
authors: Manuel
authors: M
authors: Serrano
authors: Fernando
authors: F
authors: Casares
authors: José Luis
authors: JL
authors: Gómez-Skarmeta
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