دورية أكاديمية
A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.
| العنوان: | A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs. |
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| المؤلفون: | Venema WJ; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Hiddingh S; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Loosdregt J; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Bowes J; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK., Balliu B; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., de Boer JH; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Ossewaarde-van Norel J; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Thompson SD; Department of Pediatrics, University of Cincinnati College of Medicine, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Langefeld CD; Department of Biostatistics and Data Science, and Center for Precision Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA., de Ligt A; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van der Veken LT; Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Krijger PHL; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., de Laat W; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands., Kuiper JJW; Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: j.j.w.kuiper@umcutrecht.nl. |
| المصدر: | Cell genomics [Cell Genom] 2024 Jan 10; Vol. 4 (1), pp. 100460. Date of Electronic Publication: 2023 Dec 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 9918284260106676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-979X (Electronic) Linking ISSN: 2666979X NLM ISO Abbreviation: Cell Genom Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Elsevier, Inc., [2021]- |
| مواضيع طبية MeSH: | Polymorphism, Single Nucleotide*/genetics , Autoimmune Diseases*/genetics, Humans ; Genetic Predisposition to Disease/genetics ; Promoter Regions, Genetic/genetics ; Aminopeptidases/genetics |
| مستخلص: | Single-nucleotide polymorphisms (SNPs) near the ERAP2 gene are associated with various autoimmune conditions, as well as protection against lethal infections. Due to high linkage disequilibrium, numerous trait-associated SNPs are correlated with ERAP2 expression; however, their functional mechanisms remain unidentified. We show by reciprocal allelic replacement that ERAP2 expression is directly controlled by the splice region variant rs2248374. However, disease-associated variants in the downstream LNPEP gene promoter are independently associated with ERAP2 expression. Allele-specific conformation capture assays revealed long-range chromatin contacts between the gene promoters of LNPEP and ERAP2 and showed that interactions were stronger in patients carrying the alleles that increase susceptibility to autoimmune diseases. Replacing the SNPs in the LNPEP promoter by reference sequences lowered ERAP2 expression. These findings show that multiple SNPs act in concert to regulate ERAP2 expression and that disease-associated variants can convert a gene promoter region into a potent enhancer of a distal gene. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ERAP2; GWAS; SNP; alternative splicing; autoimmunity; birdshot; eQTL; haplotype; rs2248374 |
| المشرفين على المادة: | EC 3.4.11.- (ERAP2 protein, human) EC 3.4.11.- (Aminopeptidases) |
| تواريخ الأحداث: | Date Created: 20240108 Date Completed: 20240209 Latest Revision: 20240209 |
| رمز التحديث: | 20240209 |
| مُعرف محوري في PubMed: | PMC10794781 |
| DOI: | 10.1016/j.xgen.2023.100460 |
| PMID: | 38190099 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2666-979X |
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| DOI: | 10.1016/j.xgen.2023.100460 |