Chromatin Capture Identifies SCARB1-LAG3 Proinflammatory Cardiovascular Disease Gene Networks [4C-Seq]

Purpose: Isolating chromatin interactions from a specific viewpoint, we utilized Next-generation sequencing (NGS) to profile specific chromatin interaction differences between two populations, a selected carrier (C) alele of SNP (rs10846744) associated with cardiovascular disease (CVD) and a selected non-carrier (G) allele. Methods: Chromatin was isolated from two subjects, one homozygous for the rs10846744 reference (G) allele and one homozygous for the rs10846744 risk (C) allele, processed for 4C-Seq (van de Werken et al., 2012). Results: 4C-ker (Raviram et al, 2016) analyzed the chromatin interaction data from the specific viewpoint. The results were visualized using the Washington University EpiGenome Browser (Zhou and Wang, 2013). Conclusions: Our study represents the first detailed analysis of significant changes in gene expression by an altered chromatin interaction network from SCARB1 to NR2F2 and LAG3, contributing to CAD proinflammatory gene networks. Reference (GG) cells were compared to Risk (CC) cells from the SCARB1 rs10846744 (1A) and LAG3 (2A) viewpoints, in duplicates

一、研究目的：本研究旨在从特定视角分离染色质相互作用，利用下一代测序（Next-generation sequencing, NGS）分析两个群体间的特异性染色质相互作用差异——即与心血管疾病（cardiovascular disease, CVD）相关的单核苷酸多态性（Single Nucleotide Polymorphism, SNP）rs10846744的携带型等位基因（C）与非携带型等位基因（G）之间的差异。二、研究方法：从两名受试者体内分离染色质，其中一名为rs10846744参考等位基因（G）的纯合子，另一名为rs10846744风险等位基因（C）的纯合子；随后对样本开展4C测序（4C-Seq）分析（van de Werken等，2012）。三、研究结果：采用4C-ker（Raviram等，2016）对该特定视角下的染色质相互作用数据进行分析，并通过华盛顿大学表观基因组浏览器（Washington University EpiGenome Browser, Zhou与Wang，2013）完成结果可视化。四、研究结论：本研究首次详细解析了由SCARB1至NR2F2与LAG3的染色质相互作用网络改变所介导的基因表达显著变化，该变化参与调控冠状动脉疾病（coronary artery disease, CAD）相关促炎基因网络。同时，本研究以重复实验的方式，分别从SCARB1 rs10846744（1A）与LAG3（2A）两个视角，对参考型（GG）细胞与风险型（CC）细胞开展了对比分析。