Uvarova A N, Tkachenko E A, Stasevich E M, Bogomolova E A, Zheremyan E A, Kuprash D V, Korneev K V
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Mol Biol (Mosk). 2024 Mar-Apr;58(2):270-281.
The complement inhibitor CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity in influenza A infection and vascular complications in pathologies that involve excessive activation of the complement system. A luciferase reporter system was used to functionally analyze the single nucleotide polymorphism rs2564978 in the U937 human promonocytic cell line. The polymorphism is in the promoter of the CD55 gene, and its minor allele T is associated with a severe course of influenza A(H1N1)pdm09. A decreased activity of the CD55 promoter carrying the minor rs2564978(T) allele was observed in activated U937 cells, which provide a cell model of human macrophages. Using bioinformatics resources, PU.1 was identified as a potential transcription factor that may bind to the CD55 promoter at the rs2564978 site in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was verified by a PU.1 genetic knockdown with small interfering RNAs under specific monocyte activation conditions.
补体抑制剂CD55/衰变加速因子（DAF）在多种细胞类型上表达。CD55表达失调与甲型流感感染时疾病严重程度增加以及涉及补体系统过度激活的病理状态下的血管并发症相关。利用荧光素酶报告系统对人U937前单核细胞系中的单核苷酸多态性rs2564978进行功能分析。该多态性位于CD55基因的启动子区域，其次要等位基因T与甲型（H1N1）pdm09流感的严重病程相关。在活化的U937细胞（提供人类巨噬细胞的细胞模型）中，观察到携带次要rs2564978（T）等位基因的CD55启动子活性降低。利用生物信息学资源，PU.1被鉴定为一种潜在的转录因子，它可能以等位基因特异性方式结合于rs2564978位点的CD55启动子。在特定单核细胞活化条件下，通过小干扰RNA对PU.1进行基因敲低，验证了PU.1参与调节CD55启动子活性。
