Straightforward protocol for allele-specific chromatin conformation capture

A key advance in our understanding of gene regulation came with the finding that the genome undergoes three-dimensional nuclear folding in a genetically determined process. This 3D conformation directly influences the association between enhancers and their target promoters. This complex interplay has been proven to be essential for gene regulation, and genetic variants affecting this process have been associated to human diseases. The development of new technologies that quantify these DNA interactions represented a revolution in the field. High throughput techniques like HiC provide a general picture of chromatin topology. However, they often lack resolution to evidence subtle effects that single nucleotide polymorphisms exert over the contacts between cis regulatory regions and target promoters. Here we propose a cost-efficient approach to perform allele-specific chromatin conformation analysis. As a proof of concept, we analyzed the impact of a common deletion mapping between SIRPB1 promoter and one of its downstream enhancers.

Automated summary

A key advance in understanding gene regulation is the discovery of three-dimensional nuclear folding in the genome, influencing enhancer-promoter interactions. New technologies quantifying these DNA interactions have revolutionized the field, but may lack resolution for subtle effects of single nucleotide polymorphisms. The impact of a common deletion between the SIRPB1 promoter and one of its downstream enhancers was analyzed as proof of concept for a cost-efficient allele-specific chromatin conformation analysis approach.