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.
Highlights
Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping
Physical interactions between enhancers and promoters can be identified by chromosome conformation capture (3C2)-based methods, which are performed through the digestion and re-ligation of fixated chromatin followed by enumeration of ligation junctions[3]
Hi-C7 enables the detection of long-range interactions on a genome-wide scale, its effective resolution, which is contingent on restriction fragments and experimental sensitivity, prohibits the characterization of specific interactions
Summary
Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping. 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. Hi-C7 enables the detection of long-range interactions on a genome-wide scale, its effective resolution, which is contingent on restriction fragments and experimental sensitivity, prohibits the characterization of specific interactions. Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that are associated with complex diseases As far as they have been deciphered these SNPs reside within regulatory elements and exert effects through long-range regulation of gene expression[8,9,10]. We apply cHi-C to 14 colorectal cancer (CRC) risk loci[11,12,13,14,15,16,17] to identify key long-range chromatin interactions involving these regions
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