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Nat Struct Mol Biol. 2011 Jun;18(6):708-14. doi: 10.1038/nsmb.2059. Epub 2011 May 22.

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

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  • 1Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.

Erratum in

  • Nat Struct Mol Biol. 2011 Sep;18(9):1084.

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.

PMID:
21602820
[PubMed - indexed for MEDLINE]
PMCID:
PMC3196567
Free PMC Article

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