biostudies-literatureGopalakrishnan JNational Institute of Allergy and Infectious DiseasesNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAID NIH HHSPresbyterian Health FoundationNIAMS NIH HHSNIHNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHS163-173https://www.ebi.ac.uk/biostudies/studies/S-EPMC8712360biostudies-literatureUnknown74(1)<h4>Objective</h4>Genetic variants spanning UBE2L3 are associated with increased expression of the UBE2L3-encoded E2 ubiquitin-conjugating enzyme H7 (UbcH7), which facilitates activation of proinflammatory NF-κB signaling and susceptibility to autoimmune diseases. We undertook this study to delineate how genetic variants carried on the UBE2L3/YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression.<h4>Methods</h4>We used bioinformatic analyses, electrophoretic mobility shift assays, and luciferase reporter assays to identify and functionally characterize allele-specific effects of risk variants positioned in chromatin accessible regions of immune cells. Chromatin conformation capture with quantitative polymerase chain reaction (3C-qPCR), chromatin immunoprecipitatioArthritis & rheumatology (Hoboken, N.J.)Variants on the UBE2L3/YDJC Autoimmune Disease Risk Haplotype Increase UBE2L3 Expression by Modulating CCCTC-Binding Factor and YY1 Binding.PMC8712360P30 GM110766U54 GM104938R01-AR-063124UM1 AI144292P30-AR-073750P30‐AR‐073750R01-AR-073606U54‐GM‐104938R01-AR-056360R01‐AR‐063124R01 AR056360U19 AI082714UM1-AI-144292R01 AR063124R01‐AR‐073606UM1‐AI‐144292P30 AR073750P30‐GM‐110766R01 AR073606U54-GM-104938P30-GM-110766U19‐AI‐082714U19-AI-082714R01‐AR‐056360Pasula SFu YGopalakrishnan JKelly JAPelikan RCWiley GBGaffney PMTessneer KLfalseVariants on the UBE2L3/YDJC Autoimmune Disease Risk Haplotype Increase UBE2L3 Expression by Modulating CCCTC-Binding Factor and YY1 Binding.<h4>Objective</h4>Genetic variants spanning UBE2L3 are associated with increased expression of the UBE2L3-encoded E2 ubiquitin-conjugating enzyme H7 (UbcH7), which facilitates activation of proinflammatory NF-κB signaling and susceptibility to autoimmune diseases. We undertook this study to delineate how genetic variants carried on the UBE2L3/YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression.<h4>Methods</h4>We used bioinformatic analyses, electrophoretic mobility shift assays, and luciferase reporter assays to identify and functionally characterize allele-specific effects of risk variants positioned in chromatin accessible regions of immune cells. Chromatin conformation capture with quantitative polymerase chain reaction (3C-qPCR), chromatin immunoprecipitatio2022-01-01T00:00:00Z2022 Jan2026-05-09T22:32:44.991Z2024-12-03T22:57:37.19ZS-EPMC87123603427904210.1002/art.41925