Cargando…

A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1

BACKGROUND: Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR genes polymorphisms with disease susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensive...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, XiaoYan, Chen, Zixuan, Murani, Eduard, D’Alessandro, Enrico, An, Yalong, Chen, Cai, Li, Kui, Galeano, Grazia, Wimmers, Klaus, Song, Chengyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375133/
https://www.ncbi.nlm.nih.gov/pubmed/34407874
http://dx.doi.org/10.1186/s13100-021-00248-w
_version_ 1783740259545120768
author Wang, XiaoYan
Chen, Zixuan
Murani, Eduard
D’Alessandro, Enrico
An, Yalong
Chen, Cai
Li, Kui
Galeano, Grazia
Wimmers, Klaus
Song, Chengyi
author_facet Wang, XiaoYan
Chen, Zixuan
Murani, Eduard
D’Alessandro, Enrico
An, Yalong
Chen, Cai
Li, Kui
Galeano, Grazia
Wimmers, Klaus
Song, Chengyi
author_sort Wang, XiaoYan
collection PubMed
description BACKGROUND: Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR genes polymorphisms with disease susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs), as a new type of molecular markers developed recently, have great potential in population genetics and quantitative trait locus mapping. In this study, bioinformatic prediction combined with PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution was examined, and for one RIP the impact on gene activity and phenotype was further evaluated. RESULTS: Five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, were identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was shown to act as an enhancer increasing the activities of TLR6 putative promoter and two mini-promoters. Furthermore, real-time quantitative polymerase chain reaction (qPCR) analysis revealed significant association (p < 0.05) of the ERV insertion with increased mRNA expression of TLR6, the neighboring gene TLR1, and genes downstream in the TLR signaling pathway such as MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) as well as the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in tissues of 30 day-old piglet. In addition, serum IL6 and TNFα concentrations were also significantly upregulated by the ERV insertion (p < 0.05). CONCLUSIONS: A total of five RIPs were identified in five different TLR loci. The 192 bp ERV insertion in the first intron of TLR6 was associated with higher expression of TLR6, TLR1, and several genes downstream in the signaling cascade. Thus, the ERV insertion may act as an enhancer affecting regulation of the TLR signaling pathways, and can be potentially applied in breeding of disease resistant animals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13100-021-00248-w.
format Online
Article
Text
id pubmed-8375133
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-83751332021-08-19 A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1 Wang, XiaoYan Chen, Zixuan Murani, Eduard D’Alessandro, Enrico An, Yalong Chen, Cai Li, Kui Galeano, Grazia Wimmers, Klaus Song, Chengyi Mob DNA Research BACKGROUND: Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR genes polymorphisms with disease susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs), as a new type of molecular markers developed recently, have great potential in population genetics and quantitative trait locus mapping. In this study, bioinformatic prediction combined with PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution was examined, and for one RIP the impact on gene activity and phenotype was further evaluated. RESULTS: Five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, were identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was shown to act as an enhancer increasing the activities of TLR6 putative promoter and two mini-promoters. Furthermore, real-time quantitative polymerase chain reaction (qPCR) analysis revealed significant association (p < 0.05) of the ERV insertion with increased mRNA expression of TLR6, the neighboring gene TLR1, and genes downstream in the TLR signaling pathway such as MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) as well as the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in tissues of 30 day-old piglet. In addition, serum IL6 and TNFα concentrations were also significantly upregulated by the ERV insertion (p < 0.05). CONCLUSIONS: A total of five RIPs were identified in five different TLR loci. The 192 bp ERV insertion in the first intron of TLR6 was associated with higher expression of TLR6, TLR1, and several genes downstream in the signaling cascade. Thus, the ERV insertion may act as an enhancer affecting regulation of the TLR signaling pathways, and can be potentially applied in breeding of disease resistant animals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13100-021-00248-w. BioMed Central 2021-08-18 /pmc/articles/PMC8375133/ /pubmed/34407874 http://dx.doi.org/10.1186/s13100-021-00248-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, XiaoYan
Chen, Zixuan
Murani, Eduard
D’Alessandro, Enrico
An, Yalong
Chen, Cai
Li, Kui
Galeano, Grazia
Wimmers, Klaus
Song, Chengyi
A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title_full A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title_fullStr A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title_full_unstemmed A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title_short A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1
title_sort 192 bp erv fragment insertion in the first intron of porcine tlr6 may act as an enhancer associated with the increased expressions of tlr6 and tlr1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375133/
https://www.ncbi.nlm.nih.gov/pubmed/34407874
http://dx.doi.org/10.1186/s13100-021-00248-w
work_keys_str_mv AT wangxiaoyan a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT chenzixuan a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT muranieduard a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT dalessandroenrico a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT anyalong a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT chencai a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT likui a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT galeanograzia a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT wimmersklaus a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT songchengyi a192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT wangxiaoyan 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT chenzixuan 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT muranieduard 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT dalessandroenrico 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT anyalong 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT chencai 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT likui 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT galeanograzia 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT wimmersklaus 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1
AT songchengyi 192bpervfragmentinsertioninthefirstintronofporcinetlr6mayactasanenhancerassociatedwiththeincreasedexpressionsoftlr6andtlr1