title: Chromosome conformation capture uncovers potential genome-wide interactions between human conserved non-coding sequences.
abstract: Comparative analyses of various mammalian genomes have identified numerous conserved non-coding (CNC) DNA elements that display striking conservation among species, suggesting that they have maintained specific functions throughout evolution. CNC function remains poorly understood, although recent studies have identified a role in gene regulation. We hypothesized that the identification of genomic loci that interact physically with CNCs would provide information on their functions. We have used circular chromosome conformation capture (4C) to characterize interactions of 10 CNCs from human chromosome 21 in K562 cells. The data provide evidence that CNCs are capable of interacting with loci that are enriched for CNCs. The number of trans interactions varies among CNCs; some show interactions with many loci, while others interact with few. Some of the tested CNCs are capable of driving the expression of a reporter gene in the mouse embryo, and associate with the oligodendrocyte genes OLIG1 and OLIG2. Our results underscore the power of chromosome conformation capture for the identification of targets of functional DNA elements and raise the possibility that CNCs exert their functions by physical association with defined genomic regions enriched in CNCs. These CNC-CNC interactions may in part explain their stringent conservation as a group of regulatory sequences.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Geneva, Switzerland. Daniel.Robyr@unige.ch
authors.forename: Daniel
authors.initials: D
authors.lastname: Robyr
authors.forename: Marc
authors.initials: M
authors.lastname: Friedli
authors.forename: Corinne
authors.initials: C
authors.lastname: Gehrig
authors.forename: Mélanie
authors.initials: M
authors.lastname: Arcangeli
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marin
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Laurent
authors.initials: L
authors.lastname: Farinelli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Barde
authors.forename: Sonia
authors.initials: S
authors.lastname: Verp
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D000818:Animals; D001483:Base Sequence; D002877:Chromosomes, Human / Q000737:chemistry* / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D004270:DNA, Circular / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D019901:Locus Control Region / Q000235:genetics; D051379:Mice; D009690:Nucleic Acid Conformation; D009836:Oligodendroglia / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: D004270:DNA, Circular; D021901:DNA, Intergenic; D055544:beta-Globins