HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.

HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in...

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Autores principales:	Benrong Liu, Yonggui Fu, Zhifen Wang, Sisi Zhou, Yu Sun, Yuping Wu, Anlong Xu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2264ffdb5f524596994afb5d49ec9a12
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spelling	oai:doaj.org-article:2264ffdb5f524596994afb5d49ec9a122021-11-18T07:36:20ZHLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.1932-620310.1371/journal.pone.0025794https://doaj.org/article/2264ffdb5f524596994afb5d49ec9a122011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028790/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3'-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3'-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3'-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4), and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3'-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3'-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3'-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3'-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3'-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes.Benrong LiuYonggui FuZhifen WangSisi ZhouYu SunYuping WuAnlong XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e25794 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benrong Liu Yonggui Fu Zhifen Wang Sisi Zhou Yu Sun Yuping Wu Anlong Xu HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
description	HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3'-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3'-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3'-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4), and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3'-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3'-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3'-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3'-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3'-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes.
format	article
author	Benrong Liu Yonggui Fu Zhifen Wang Sisi Zhou Yu Sun Yuping Wu Anlong Xu
author_facet	Benrong Liu Yonggui Fu Zhifen Wang Sisi Zhou Yu Sun Yuping Wu Anlong Xu
author_sort	Benrong Liu
title	HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
title_short	HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
title_full	HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
title_fullStr	HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
title_full_unstemmed	HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.
title_sort	hla-drb1 may be antagonistically regulated by the coordinately evolved promoter and 3'-utr under stabilizing selection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/2264ffdb5f524596994afb5d49ec9a12
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HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.

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