Cited by 492Genomics and Chromatin DynamicsChromatin Remodeling and CancerGenetic Associations and Epidemiology

Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment

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Hughes, Jim R, Roberts, Nigel, McGowan, Simon, Hay, Deborah, Giannoulatou, Eleni, Lynch, Magnus, De Gobbi, Marco, Taylor, Stephen +2 more·2014·Nature Genetics

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.

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Crossref · 10.1038/ng.2871

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Authors
Hughes, J. R., Roberts, N., McGowan, S., Hay, D., Giannoulatou, E., Lynch, M., De Gobbi, M., Taylor, S., Gibbons, R., & Higgs, D. R.
Affiliations
University of Oxford (GB)
Corresponding author
  • Hughes, Jim R
  • Higgs, Douglas R
Venue
Nature Genetics
Published
2014-01-12
Volume
46
Issue
2
Pages
205-212
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W1974223852
Cited by
461
References
53
Citations by year
2026: 11 · 2025: 11 · 2024: 29 · 2023: 38 · 2022: 31 · 2021: 50 · 2020: 53 · 2019: 50 · 2018: 48 · 2017: 40 · 2016: 43 · 2015: 38 · 2014: 18
FWCI
17.49
Type
journal article
Language
en
Open access
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (91070, 090532, 090532/Z/09/Z, 090532/Z/09/, 090532/Z)
  • Medical Research Council (G0900747 91070, 090532/Z09/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
cis-regulatory elements, chromosome conformation capture, enhancers, silencers, boundary elements, promoter, gene expression regulation, single nucleotide polymorphisms, complex disease genetics, target gene identification
MeSH terms
Animals, Base Sequence, Female, Humans, Molecular Sequence Data, Gene Library, Sequence Analysis, DNA, Gene Expression Regulation, Developmental, Polymorphism, Single Nucleotide, Genetic Diseases, Inborn, Chromatin Immunoprecipitation, Regulatory Elements, Transcriptional, Mice, High-Throughput Screening Assays

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