Department of Medicine, Division of Clinical Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, ZIP Code 14.049-900, Brazil.
Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, ZIP code 75010, France.
Sci Rep. 2018 Apr 4;8(1):5652. doi: 10.1038/s41598-018-24009-7.
The HLA-G 5'URR extending 1.4 kb from the ATG presents a unique set of regulatory elements among HLA genes. Several variable sites have been described that coincide with or are close to these elements, thus HLA-G 5'URR polymorphism might influence the HLA-G expression level. We cloned the ten most frequent HLA-G 5'URR haplotypes to evaluate their activity on a luciferase reporter gene in HLA-G cell lines (JEG-3/choriocarcinoma and FON/melanoma). We also investigated associations between the plasma HLA-G (sHLA-G) levels and the HLA-G 5'URR variability in 157 healthy individuals. Cell lines were transfected with pGL3-Basic vector constructions containing HLA-G 5'URR sequences. The G010101a (in JEG-3) and G010101b (in FON) haplotypes exhibited higher promoter activity, whereas the G010101d (in JEG-3) and G010102a (in FON) haplotypes exhibited lower promoter activity. In the presence of HLA-G inducers (interferon-β and progesterone) or repressors (cyclopamine) HLA-G promoter activity was modulated, but certain haplotypes exhibited differential responses. No strict association was observed between plasma sHLA-G levels and the 5'URR haplotypes or genotypes; however, the G010101b haplotype was underrepresented among HLA-G-negative plasmas. Therefore, the HLA-G 5'URR polymorphism may have an impact on the modulation of HLA-G gene expression, but alone provides a limited predictive value for sHLA-G levels in vivo.
HLA-G 5'URR 从 ATG 延伸 1.4kb，在 HLA 基因中呈现出一组独特的调节元件。已经描述了几个可变位点，这些位点与这些元件重合或接近，因此 HLA-G 5'URR 多态性可能影响 HLA-G 的表达水平。我们克隆了十种最常见的 HLA-G 5'URR 单倍型，以评估它们在 HLA-G 细胞系（JEG-3/绒毛膜癌和 FON/黑色素瘤）中对荧光素酶报告基因的活性。我们还研究了 157 名健康个体血浆 HLA-G（sHLA-G）水平与 HLA-G 5'URR 变异性之间的关系。细胞系用含有 HLA-G 5'URR 序列的 pGL3-Basic 载体构建体转染。G010101a（在 JEG-3 中）和 G010101b（在 FON 中）单倍型表现出更高的启动子活性，而 G010101d（在 JEG-3 中）和 G010102a（在 FON 中）单倍型表现出更低的启动子活性。在存在 HLA-G 诱导剂（干扰素-β和孕酮）或抑制剂（环巴胺）的情况下，HLA-G 启动子活性被调节，但某些单倍型表现出不同的反应。在血浆 sHLA-G 水平与 5'URR 单倍型或基因型之间未观察到严格的相关性；然而，G010101b 单倍型在 HLA-G 阴性血浆中代表性不足。因此，HLA-G 5'URR 多态性可能对 HLA-G 基因表达的调节有影响，但单独对体内 sHLA-G 水平的预测价值有限。
