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

David Martin, Cristina Pantoja, Ana Fernández Miñán, Christian Valdes-Quezada, Eduardo Moltó, Fuencisla Matesanz, Ozren Bogdanović, Elisa de la Calle-Mustienes, Orlando Domínguez, Leila Taher, Mayra Furlan-Magaril, Antonio Alcina, Susana Cañón, María Fedetz, María A Blasco, Paulo S Pereira, Ivan Ovcharenko, Félix Recillas-Targa, Lluís Montoliu, Miguel ManzanaresRoderic Guigó, Manuel Serrano, Fernando Casares*, José Luis Gómez-Skarmeta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)708-14
Number of pages7
JournalNature Structural & Molecular Biology
Issue number6
Publication statusPublished - Jun 2011


  • Animals
  • CCCTC-Binding Factor
  • Cell Line
  • Chickens
  • Conserved Sequence
  • DNA/metabolism
  • DNA-Binding Proteins/genetics
  • Genome
  • Humans
  • Mice
  • Multiple Sclerosis/pathology
  • Nuclear Proteins/genetics
  • Polymorphism, Genetic
  • Protein Binding
  • Repressor Proteins/metabolism
  • Transcription Factors/genetics


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