Identifying cancer risk loci is like trying to find a key you lost somewhere in your apartment. You know that it’s there and by combining experience with indistinct recollection you can even narrow it down to a few square meters. Now imagine you not only have to find the key but also map all the items it came in contact with. This was the situation a group of international researchers led by Richard S. Houlston were facing when they set out to map the chromatin interactome of colorectal cancer (CRC) risk loci.
The main problem is that locus specific chromatin conformation capture methods such as 4C require precise knowledge of the target location, but cancer risk loci identified by genome-wide association studies (GWAS) are often not so well defined.
Genome-wide approaches such as Hi-C, on the other hand, lack the sensitivity necessary for the characterization of locus specific interactions. To solve this dilemma, the researchers came up with a clever solution: using specific RNA baits to enrich target loci in a Hi-C library. Calling this new tool capture Hi-C (cHi-C), they set out to study the chromatin interactome at 14 CRC risk loci. Here is what they found:
- cHi-C produces high resolution chromatin interactomes of target loci (9 kb for all 14 loci, 3 kb for 9 risk loci).
- cHi-C at CRC risk loci identified long-range cis-interactions as well as evidence for interchromosomal trans-interactions.
- Besides confirming documented interactions, cHi-C revealed novel interactions of CRC risk loci with long non-coding RNAs, known oncogenes and regions encoding uncharacterized proteins.
- Chromatin contacts within the CRC risk interactome preferentially map to regulatory elements.
From this the researchers conclude that cHi-C allows the unbiased identification of interacting regions of a target locus at a higher resolution and cost-effectiveness than conventional Hi-C methods.
So halt the hunt for your keys and head over to Nature Communications, February 2015.