Journal article
Wide-spread enhancer effect of SNP rs2279590 on regulating epoxide hydrolase-2 and protein tyrosine kinase 2-beta gene expression
Gene, Vol.854, p.147096
02/20/2023
DOI: 10.1016/j.gene.2022.147096
PMID: 36470481
Abstract
Polymorphisms in the PTK2B-CLU locus have been associated with various neurodegenerative disorders including pseudoexfoliation glaucoma, Alzheimer's and Parkinson's. Many of these genomic variants are within enhancer elements and modulate genes associated with the disease pathogenesis. However, mechanisms by which they control the gene expression is unknown. Previously, we have shown that clusterin enhancer element surrounding rs2279590 intronic variant, a risk factor in the pathogenesis of pseudoexfoliation glaucoma mod-ulates gene expression of clusterin (CLU), protein tyrosine kinase 2 beta (PTK2B) and epoxide hydrolase 2 (EPHX2). Here, we explored the mechanism by which rs2279590 enhancer regulates their gene expression through chromosome conformation capture assays. 3C assays revealed a strong enhancer-promoter chromatin interaction between rs2279590 enhancer and promoters of genes CLU, PTK2B and EPHX2 in the HEK293 wild type cells. Moreover, genomic knockout of rs2279590 element significantly decreases the chromatin-chromatin cross-linking frequency suggesting gene regulation at transcriptional level through formation of chromatin loop. In addition, molecular assays showed a significantly decreased expression of EPHX2 but not PTK2B at both mRNA and protein level in the lens capsule of pseudoexfoliation affected patients in comparison to control subjects implying a role of EPHX2 in the pathogenesis of pseudoexfoliation.
Details
- Title: Subtitle
- Wide-spread enhancer effect of SNP rs2279590 on regulating epoxide hydrolase-2 and protein tyrosine kinase 2-beta gene expression
- Creators
- Biswajit Padhy - National Institute of Science Education and ResearchRamani Shyam Kapuganti - National Institute of Science Education and ResearchBushra Hayat - National Institute of Science Education and ResearchPranjya Paramita Mohanty - Sri Sri Borda Hosp, Bhubaneswar 751002, Odisha, IndiaDebasmita Pankaj Alone - National Institute of Science Education and Research
- Resource Type
- Journal article
- Publication Details
- Gene, Vol.854, p.147096
- DOI
- 10.1016/j.gene.2022.147096
- PMID
- 36470481
- ISSN
- 0378-1119
- eISSN
- 1879-0038
- Publisher
- Elsevier
- Number of pages
- 8
- Language
- English
- Date published
- 02/20/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985157628102771
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