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.

我们对基因调控的理解取得了重大进展，发现基因组在遗传决定的过程中经历了三维核折叠。这种 3D 构象直接影响增强子与其目标启动子之间的关联。这种复杂的相互作用已被证明对基因调控至关重要，影响这一过程的遗传变异与人类疾病有关。量化这些 DNA 相互作用的新技术的发展代表了该领域的一场革命。像 HiC 这样的高通量技术提供了染色质拓扑的一般情况。然而，他们通常缺乏分辨率来证明单核苷酸多态性对顺式之间的接触产生的微妙影响。-调节区域和目标启动子。在这里，我们提出了一种经济高效的方法来进行等位基因特异性染色质构象分析。作为概念证明，我们分析了SIRPB1启动子与其下游增强子之一之间常见缺失映射的影响。