A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models.

Hall, Ashley, Middlehurst, Ben ORCID: 0000-0002-2603-2719, Cadogan, Max AM, Reed, Xylena, Billingsley, Kimberley J, Bubb, Vivien J ORCID: 0000-0003-2763-7004 and Quinn, John P ORCID: 0000-0003-3551-7803 (2024) A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models. Scientific reports, 14 (1). p. 792. ISSN 2045-2322, 2045-2322

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Chromatin, Humans, Membrane Glycoproteins, Retroelements, Gene Expression, Short Interspersed Nucleotide Elements, Clustered Regularly Interspaced Short Palindromic Repeats
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	25 Jan 2024 09:04
Last Modified:	28 Feb 2026 04:20
DOI:	10.1038/s41598-023-50307-w
Open Access URL:	https://doi.org/10.1038/s41598-023-50307-w
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178000
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