Promoter-focused chromatin conformation techniques directly detect interactions between gene promoters and distal genomic sequences, providing structural information relevant to gene regulation without the excessive non-genic architectural data generated by full-scale Hi-C. 3D promoter ‘interactome’ maps are crucial for understanding how epigenomic features such as histone modifications and open chromatin, or genetic variants identified in genome-wide association studies (GWAS), contribute to biological function. However, variation in sensitivity between such promoter-focused methods, principally due to restriction enzyme selection, has not been systematically assessed. Here, we performed a head-to-head comparison of promoter capture datasets using 4 cutters (DpnII or MboI) versus the 6 cutter HindIII from the same five cell types. While HindIII generally produces a higher signal-to-noise ratio for significant interactions in comparison to 4-cutters, we show that DpnII/MboI detects more proximal interactions and shows little overlap with the HindIII detection range. Promoter-interacting genomic regions mapped by 4-cutters are more enriched for regulatory features and disease-associated genetic variation than 6-cutters maps, suggesting that high-resolution maps better capture gene regulatory architectures than do lower resolution approaches.

以启动子为中心的染色质构象技术直接检测基因启动子和远端基因组序列之间的相互作用，提供与基因调控相关的结构信息，而无需全尺寸 Hi-C 生成的过多非基因结构数据。3D 启动子“相互作用组”图对于了解组蛋白修饰和开放染色质等表观基因组特征或全基因组关联研究 (GWAS) 中鉴定的遗传变异如何促进生物学功能至关重要。然而，这种以启动子为重点的方法之间的敏感性差异，主要是由于限制性内切酶的选择，尚未得到系统评估。在这里，我们使用 4 个切割器（DpnII 或 MboI）与来自相同五种细胞类型的 6 个切割器 HindIII 对启动子捕获数据集进行了头对头比较。虽然与 4 切割器相比，HindIII 通常会为显着相互作用产生更高的信噪比，但我们表明 DpnII/MboI 检测到更多的近端相互作用，并且与 HindIII 检测范围几乎没有重叠。与 6 切割图相比，由 4 切割图绘制的启动子相互作用基因组区域的调控特征和疾病相关遗传变异更丰富，这表明高分辨率图比低分辨率方法更好地捕获基因调控结构。