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The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses

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 f...

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Autores principales: Dias, Fabrício C., Bertol, Bruna C., Poras, Isabelle, Souto, Bruno M., Mendes-Junior, Celso T., Castelli, Erick C., Gineau, Laure, Sabbagh, Audrey, Rouas-Freiss, Nathalie, Carosella, Edgardo D., Donadi, Eduardo A., Moreau, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884815/
https://www.ncbi.nlm.nih.gov/pubmed/29618829
http://dx.doi.org/10.1038/s41598-018-24009-7
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author Dias, Fabrício C.
Bertol, Bruna C.
Poras, Isabelle
Souto, Bruno M.
Mendes-Junior, Celso T.
Castelli, Erick C.
Gineau, Laure
Sabbagh, Audrey
Rouas-Freiss, Nathalie
Carosella, Edgardo D.
Donadi, Eduardo A.
Moreau, Philippe
author_facet Dias, Fabrício C.
Bertol, Bruna C.
Poras, Isabelle
Souto, Bruno M.
Mendes-Junior, Celso T.
Castelli, Erick C.
Gineau, Laure
Sabbagh, Audrey
Rouas-Freiss, Nathalie
Carosella, Edgardo D.
Donadi, Eduardo A.
Moreau, Philippe
author_sort Dias, Fabrício C.
collection PubMed
description 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.
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spelling pubmed-58848152018-04-09 The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses Dias, Fabrício C. Bertol, Bruna C. Poras, Isabelle Souto, Bruno M. Mendes-Junior, Celso T. Castelli, Erick C. Gineau, Laure Sabbagh, Audrey Rouas-Freiss, Nathalie Carosella, Edgardo D. Donadi, Eduardo A. Moreau, Philippe Sci Rep Article 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. Nature Publishing Group UK 2018-04-04 /pmc/articles/PMC5884815/ /pubmed/29618829 http://dx.doi.org/10.1038/s41598-018-24009-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dias, Fabrício C.
Bertol, Bruna C.
Poras, Isabelle
Souto, Bruno M.
Mendes-Junior, Celso T.
Castelli, Erick C.
Gineau, Laure
Sabbagh, Audrey
Rouas-Freiss, Nathalie
Carosella, Edgardo D.
Donadi, Eduardo A.
Moreau, Philippe
The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title_full The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title_fullStr The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title_full_unstemmed The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title_short The genetic diversity within the 1.4 kb HLA-G 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
title_sort genetic diversity within the 1.4 kb hla-g 5′ upstream regulatory region moderately impacts on cellular microenvironment responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884815/
https://www.ncbi.nlm.nih.gov/pubmed/29618829
http://dx.doi.org/10.1038/s41598-018-24009-7
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