Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci

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• Migliorini, Gabriele
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• Henrion, Marc
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• Kandaswamy, Radhika
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• Speedy, Helen E.
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• Heindl, Andreas
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• Whiffin, Nicola
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• Carnicer, Maria J.
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• Broome, Laura
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• Dryden, Nicola
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• Nagano, Takashi
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• Schoenfelder, Stefan
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• Enge, Martin
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• Yuan, Yinyin
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• Taipale, Jussi
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• Fraser, Peter
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• Fletcher, Olivia
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• Houlston, Richard S.

Abstract

Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we develop a capture Hi-C (cHi-C) approach to allow an agnostic characterization of these physical interactions on a genome-wide scale. Single-nucleotide polymorphisms associated with complex diseases often reside within regulatory elements and exert effects through long-range regulation of gene expression. Applying this cHi-C approach to 14 colorectal cancer risk loci allows us to identify key long-range chromatin interactions in cis and trans involving these loci.