title: Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.
abstract: Gene expression during development and differentiation is regulated in a cell- and stage-specific manner by complex networks of intergenic and intragenic cis-regulatory elements whose numbers and representation in the genome far exceed those of structural genes. Using chromosome conformation capture, it is now possible to analyze in detail the interaction between enhancers, silencers, boundary elements and promoters at individual loci, but these techniques are not readily scalable. Here we present a high-throughput approach (Capture-C) to analyze cis interactions, interrogating hundreds of specific interactions at high resolution in a single experiment. We show how this approach will facilitate detailed, genome-wide analysis to elucidate the general principles by which cis-acting sequences control gene expression. In addition, we show how Capture-C will expedite identification of the target genes and functional effects of SNPs that are associated with complex diseases, which most frequently lie in intergenic cis-acting regulatory elements.
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Jim R
authors.initials: JR
authors.lastname: Hughes
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Roberts
authors.affiliation: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: McGowan
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hay
authors.affiliation: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Giannoulatou
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: De Gobbi
authors.affiliation: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Gibbons
authors.affiliation: Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Higgs
mesh_terms: D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015723:Gene Library; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D017422:Sequence Analysis, DNA