A&R: Variations in UBE2L3/YDJC autoimmune disease risk haplotypes increase UBE2L3 expression by modulating CCCTC-binding factor and YY1 binding

Objective: Genetic variants spanning UBE2L3 are associated with increased expression of UBE2L3 - encoded E2 ubiquitin-conjugating enzyme H7 (UbcH7) , which contributes to activation of pro-inflammatory NF-κB signaling and increased susceptibility to autoimmune disease .
We conducted this study to describe how genetic variation drives hypermorphic UBE2L3 expression (hypermorphic expression: increased levels of gene product activity, or increased horizontal expression of wild-type gene products) through UBE2L3/YDJC autoimmune risk haplotype function.
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Objective: Genetic variation across UBE2L3 UBE2L3 is associated with increased expression of UBE2L3 - encoded E2 ubiquitin-conjugating enzyme H7 (UbcH7) , which contributes to activation of pro-inflammatory NF-κB signaling and increased susceptibility to autoimmune disease .

We conducted this study to describe how genetic variation drives hypermorphic UBE2L3 UBE2L3 expression (hypermorphic expression: increased levels of gene product activity, or wild-type gene product) through UBE2L3/YDJC UBE2L3/YDJC autoimmune risk haplotype function.
increased expression .

Methods: We used bioinformatics analysis, electrophoretic mobility shift assay ( EMSA ), and luciferase reporter gene assays to identify and functionally characterize the allele-specific effects of risk variants located in accessible regions of immune cell chromatin

RESULTS: Of the 7 preferential variants, 5 exhibited allele-specific increases in nucleoprotein binding affinity and regulatory activity

Conclusion: UBE2L3/YDJC UBE2L3/YDJC autoimmune risk haplotype increases UBE2L3 UBE2L3 expression by enhancing YY1 - mediated interaction between UBE2L3 UBE2L3 and YDJC YDJC promoter .

Gopalakrishnan, J.

, Tessneer, KL, Fu, Y.
, Pasula, S.

Gopalakrishnan, J.
, Tessneer, KL, Fu, Y.
, Pasula, S.
, Pelikan, RC, Kelly, JA, Wiley, GB and Gaffney, PM (2022), Variants on the  UBE2L3 / YDJC  Autoimmune Disease Risk Haplotype Increase  UBE2L3  Expression by Modulating CCCTC-Binding Factor and YY1 Binding.
Arthritis Rheumatol, 74: 163-173.
  UBE2L3 YDJC UBE2L3 https://doi.
org/10.
1002/art.
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