Angiogenesis is extensively involved in embryonic development and requires complex regulation networks, whose defects can cause a variety of vascular abnormalities. Cis-regulatory elements control gene expression at all developmental stages, but they have not been studied or profiled in angiogenesis yet. In this study, we exploited public DNase-seq and RNA-seq datasets from a VEGFA-stimulated in vitro angiogenic model, and carried out an integrated analysis of the transcriptome and chromatin accessibility across the entire process. Totally, we generated a bank of 47,125 angiogenic cis-regulatory elements with promoter (marker by H3K4me3) and/or enhancer (marker by H3K27ac) activities. Motif enrichment analysis revealed that these angiogenic cis-regulatory elements interacted preferentially with ETS family TFs. With this tool, we performed an association study using our WES data of TAPVC and identified rs199530718 as a cis-regulatory SNP associated with disease risk. Altogether, this study generated a genome-wide bank of angiogenic cis-regulatory elements and illustrated its utility in identifying novel cis-regulatory SNPs for TAPVC, expanding new horizons of angiogenesis as well as vascular abnormality genetics.

血管生成广泛参与胚胎发育，需要复杂的调控网络，其缺陷可导致多种血管异常。顺式调节元件控制所有发育阶段的基因表达，但尚未在血管生成中研究或分析它们。在这项研究中，我们利用来自 VEGFA 刺激的体外血管生成模型的公共 DNase-seq 和 RNA-seq 数据集，并对整个过程中的转录组和染色质可及性进行了综合分析。总共，我们生成了 47,125 个具有启动子（H3K4me3 标记）和/或增强子（H3K27ac 标记）活性的血管生成顺式调节元件库。基序富集分析表明，这些血管生成顺式调节元件优先与 ETS 家族 TF 相互作用。借助该工具，我们利用 TAPVC 的 WES 数据进行了关联研究，并将 rs199530718 确定为与疾病风险相关的顺式调节 SNP。总之，这项研究生成了全基因组血管生成顺式调节元件库，并说明了其在识别 TAPVC 的新型顺式调节SNP 方面的实用性，拓展了血管生成和血管异常遗传学的新视野。