SINE-VNTR-Alu (SVA) retrotransposons represent mobile regulatory elements that have the potential to influence the surrounding genome when they insert into a locus. Evolutionarily recent mobilisation has resulted in loci in the human genome where a given retrotransposon might be observed to be present or absent, termed a retrotransposon insertion polymorphism (RIP). We previously observed that an SVA RIP ~ 2 kb upstream of LRIG2 on chromosome 1, the ‘LRIG2 SVA’, was associated with differences in local gene expression and methylation, and that the two were correlated. Here, we have used CRISPR-mediated deletion of the LRIG2 SVA in a cell line model to validate that presence of the retrotransposon is directly affecting local expression and provide evidence that is suggestive of a modest role for the SVA in modulating nearby methylation. Additionally, in leveraging an available Hi-C dataset we observed that the LRIG2 SVA was also involved in long-range chromatin interactions with a cluster of genes ~ 300 kb away, and that expression of these genes was to varying degrees associated with dosage of the SVA in both CRISPR cell line and population models. Altogether, these data support a regulatory role for SVAs in the modulation of gene expression, with the latter potentially involving chromatin looping, consistent with the model that RIPs may contribute to interpersonal differences in transcriptional networks.

SINE-VNTR- Alu (SVA) 反转录转座子代表移动调控元件，当它们插入基因座时，有可能影响周围的基因组。最近的进化动员已经在人类基因组中产生了一些位点，在这些位点中可以观察到给定的逆转录转座子存在或不存在，称为逆转录转座子插入多态性（RIP）。我们之前观察到 1 号染色体上LRIG2上游约 2 kb 的 SVA RIP，即“LRIG2 SVA”，与局部基因表达和甲基化的差异相关，并且两者是相关的。在这里，我们在细胞系模型中使用 CRISPR 介导的 LRIG2 SVA 缺失来验证逆转录转座子的存在直接影响局部表达，并提供证据表明 SVA 在调节附近甲基化方面发挥适度作用。此外，在利用可用的 Hi-C 数据集时，我们观察到 LRIG2 SVA 还参与与约 300 kb 之外的一组基因的长程染色质相互作用，并且这些基因的表达在不同程度上与CRISPR 细胞系和群体模型中的 SVA。总而言之，这些数据支持 SVA 在基因表达调节中的调节作用，后者可能涉及染色质循环，这与 RIP 可能导致转录网络中人际差异的模型一致。