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

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...

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Κύριοι συγγραφείς: Hughes, J, Roberts, N, McGowan, S, Hay, D, Giannoulatou, E, Lynch, M, De Gobbi, M, Taylor, S, Gibbons, R, Higgs, D
Μορφή: Journal article
Γλώσσα:English
Έκδοση: Nature Publishing Group 2014
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author Hughes, J
Roberts, N
McGowan, S
Hay, D
Giannoulatou, E
Lynch, M
De Gobbi, M
Taylor, S
Gibbons, R
Higgs, D
author_facet Hughes, J
Roberts, N
McGowan, S
Hay, D
Giannoulatou, E
Lynch, M
De Gobbi, M
Taylor, S
Gibbons, R
Higgs, D
author_sort Hughes, J
collection OXFORD
description 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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spelling oxford-uuid:70c4e8bd-b9fb-40a2-a40c-4052d65a48f72022-03-26T19:39:22ZAnalysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experimentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70c4e8bd-b9fb-40a2-a40c-4052d65a48f7EnglishSymplectic Elements at OxfordNature Publishing Group2014Hughes, JRoberts, NMcGowan, SHay, DGiannoulatou, ELynch, MDe Gobbi, MTaylor, SGibbons, RHiggs, DGene 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.
spellingShingle Hughes, J
Roberts, N
McGowan, S
Hay, D
Giannoulatou, E
Lynch, M
De Gobbi, M
Taylor, S
Gibbons, R
Higgs, D
Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title_full Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title_fullStr Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title_full_unstemmed Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title_short Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment
title_sort analysis of hundreds of cis regulatory landscapes at high resolution in a single high throughput experiment
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