Polymorphisms associated to bovine paratuberculosis: investigation of their role in DNA-protein interactions and transcriptional regulation
DOI:
https://doi.org/10.12834/VetIt.2325.13205.1Keywords:
Paratubercolosis, SNP, EMSA, RNA-SeqAbstract
Previous studies led to identify SNPs in putative regulatory regions of the SLC11A1 and CARD15 genes with association to paratuberculosis in cattle. Aim of this study was to investigate the role of these mutations at the regulatory level by DNA-protein interaction analyses and transcriptome comparison between wild-type and mutated animals. Gene regions carrying the SNPs of interest were analysed by bioinformatic tools to predict allele-dependent binding sites for transcription factors (TFBS). Putative TFBS were in vitro explored by Electrophoretic Mobility Shift Assays (EMSA). EMSA did not show specific gel shifts for any allele indicating that these SNPs may eventually influence gene transcription without altering TFBS. Whole transcriptome expression analysis was performed on intestinal tissues of wild-type and mutated cattle by RNA-Seq. Differential regulation of five genes involved in innate immune system was detected. Specifically, ULBP3 was down-regulated, while S100A8, S100A12, LOC510860, and IFI27 were up-regulated. In previous studies, ULBP3, S100A8, and S100A12 resulted differentially expressed in cattle affected by paratuberculosis, suggesting a possible implication in the pathogen response. Further investigations are needed to elucidate the functional role of these SNPs and to understand the gene network involved in the interactions between non-coding SNPs and other genome regions.
References
Areschoug T., Carlsson F., Stålhammar‑Carlemalm M. & Lindahl G. 2004. Host‑pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development. Vaccine, 22S, S9‑S14.
Chen H., Cheng L., Yang S., Liu X., Liu Y., Tang J., Li X. He Q. & Zhao S. 2010. Molecular characterization, induced expression, and transcriptional regulation of porcine S100A12 gene. Molecular Immunology, 47, 1601‑1607.
Chorley B.N., Wang X., Campbell M.R., Pittman G.S., Noureddine M.A. & Bell D.A. 2008. Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutat Res, 659, 147‑157.
Donato R., Cannon B., Sorci G., Riuzzi F., Hsu K., Weber D. & Geczy C. 2013. Functions of S100 proteins. Curr Mol Med, 13, 24‑57.Elkon R. & Agami R. 2017. Characterization of noncoding regulatory DNA in the human genome. Nature Biotech, 35, 732‑746.
Eltholth M.M., Marsh V.R., Van Winden S. & Guitian F.J. 2009. Contamination of food products with Mycobacterium avium paratuberculosis: a systematic review. J Appl Microbiol, 107, 1061‑1071.
Hellman L.M. & Fried M.G. 2007. Electrophoretic mobility shift assay (EMSA) for detecting protein‑nucleic acid interactions. Nat Protoc, 2 (8), 1849‑1861.Holden N.S. & Tacon C.E. 2011. Principles and problems of the electrophoretic mobility shift assay. J Pharmacol Toxicol Methods, 63, 7‑14.
Hsiao C.P., Araneta M., Wang X.M. & Saligan L.N. 2013. The association of IFI27 expression and fatigue intensification during localized radiation therapy:implication of a para‑Inflammatory bystander response. Int J Mol Sci, 14, 16943‑16957.
Hudson T.J. 2003. Wanted: regulatory SNPs. Nat Genet, 33, 439‑440.
Hugot J.P., Chamaillard M., Zouali H., Lesage S., Cézard J.P., Belaiche J., Almer S., Tysk C., O'Morain C.A., Gassull M., Binder V., Finkel Y., Cortot A., Modigliani R., Laurent‑Puig P., Gower‑Rousseau C., Macry J., Colombel J.F., Sahbatou M. & Thomas G. 2001. Association of NOD2 leucine‑rich repeat variants with susceptibility to Crohn's disease. Nature, 411, 599‑603.
Ikhtaire S., Shajib M.S., Reinisch W. & Khan W.I. 2016. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol, 51, 434‑446.
Kasahara M. & Yoshida S. 2012. Immunogenetics of the NKG2D ligand gene family. Immunogenetics, 64, 855‑867.
Korou L.M., Liandris E., Gazouli M. & Ikonomopoulos J. 2010. Investigation of the association of the SLC11A1gene with resistance/sensitivity of goats (Capra hircus) to paratuberculosis. Vet Microbiol, 144, 353‑358.
Larson J.H., Marron, B.M., Beever, J.E., Roe, B.A. & Lewin H.A. 2006. Genomic organization and evolution of the ULBPgenes in cattle. BMC Genomics, 7, 227.
McNees A.L., Markesich D., Zayyani N.R. & Graham D.Y. 2015. Mycobacterium paratuberculosis as a cause of Crohn’s disease. Expert rev Gastroenterol & Hepathol, 9, 1523‑1534.
Mendoza J.L., Lana R. & Diaz‑Rubio M. 2009. Mycobacterium avium subspecies paratuberculosis and its relationship with Chron's disease. World J Gastroenterol, 15, 417‑422.
Mou X., Zhou Y., Jiang P., Zhou T., Jiang Q., Xu C., Liu H., Zheng T., Yuan G., Zhang Y., Chen D. & Mao C. 2014. The regulatory effect of UL‑16 binding protein‑3 expressioimplication of a para‑Inflammatory bystander response. Int J Mol Sci, 14, 16943‑16957.
Hudson T.J. 2003. Wanted: regulatory SNPs. Nat Genet, 33, 439‑440.
Hugot J.P., Chamaillard M., Zouali H., Lesage S., Cézard J.P., Belaiche J., Almer S., Tysk C., O'Morain C.A., Gassull M., Binder V., Finkel Y., Cortot A., Modigliani R., Laurent‑Puig P., Gower‑Rousseau C., Macry J., Colombel J.F., Sahbatou M. & Thomas G. 2001. Association of NOD2 leucine‑rich repeat variants with susceptibility to Crohn's disease. Nature, 411, 599‑603.
Ikhtaire S., Shajib M.S., Reinisch W. & Khan W.I. 2016. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol, 51, 434‑446.
Kasahara M. & Yoshida S. 2012. Immunogenetics of the NKG2D ligand gene family. Immunogenetics, 64, 855‑867.
Korou L.M., Liandris E., Gazouli M. & Ikonomopoulos J. 2010. Investigation of the association of the SLC11A1gene with resistance/sensitivity of goats (Capra hircus) to paratuberculosis. Vet Microbiol, 144, 353‑358.
Larson J.H., Marron, B.M., Beever, J.E., Roe, B.A. & Lewin H.A. 2006. Genomic organization and evolution of the ULBPgenes in cattle. BMC Genomics, 7, 227.
McNees A.L., Markesich D., Zayyani N.R. & Graham D.Y. 2015. Mycobacterium paratuberculosis as a cause of Crohn’s disease. Expert rev Gastroenterol & Hepathol, 9, 1523‑1534.
Mendoza J.L., Lana R. & Diaz‑Rubio M. 2009. Mycobacterium avium subspecies paratuberculosis and its relationship with Chron's disease. World J Gastroenterol, 15, 417‑422.
Mou X., Zhou Y., Jiang P., Zhou T., Jiang Q., Xu C., Liu H., Zheng T., Yuan G., Zhang Y., Chen D. & Mao C. 2014. The regulatory effect of UL‑16 binding protein‑3 expressio134, 346‑352.
Pozzato N., Capello K., Comin A., Toft N., Nielsen S.S., Vincenzoni G. & Arrigoni N. 2011. Prevalence of paratuberculosis infection in dairy cattle in Nothern Italy. Prev Vet Med, 102, 83‑86.
Reddacliff L.A., Beh K., Mc Gregor H. & Whittington R.J. 2005. A preliminary study of possible genetic influences on the suceptibility of sheep to Johne's disease. Aust Vet J, 83, 435‑441.
Roupie V., Rosseels V., Piersoel V., Zinniel D.K., Barletta R.G. & Huygen K. 2012. Genetic resistance of mice to Mycobacterium paratuberculosis is influenced by SLC11A1 at the early but not at the late stage of infection. Infect Immun, 76, 2099‑2105
Ruiz‑Larrañaga O., Garrido J.M., Manzano C., Iriondo M., Molina E., Gil A., Koets A.P., Rutten V.P., Juste R.A. & Estonba A. 2010. Identification of single nucleotide polymorphisms in the bovine solute carrier family 11 member 1 (SLC11A1) gene and their association with infection by Mycobacterium avium subspecies paratuberculosis. J Dairy Sci, 4, 1713‑1721.
Shin M.K., Park H. T., Shin S.W., Jung M., Im Y.B., Park H.E., Cho Y.I. & Yoo H.S. 2015. Whole‑blood gene‑expression profiles of cows infected with Mycobacterium avium subsp. paratuberculosis reveal changes in immune response and lipid metabolism. J Microb Biotech, 25, 255‑267.
Vandal K., Rouleau P., Boivin A., Ryckman C., Talbot M. & Tessier P.A. 2003. Blockade of S100A8 and S100A9suppresses lipopolysaccharide neutrophil migration in response to lipopolysaccharide. J Immunology, 171, 2602‑2609.
Verschoor C.P., Pant S.D., You Q., Kelton D.F. & Karrow N.A. 2010. Gene expression profiling of PBMCs from Holstein and Jersey cows sub‑clinically infected with Mycobacterium avium ssp. paratuberculosis. Vet Immunol Immunopath, 137, 1‑11.
Whittington R., Donat K., Weber M.F., Kelton D., Nielsen S.S., Eisenberg S., Arrigoni N., Juste R., Sáez J.L., Dhand N., Santi A., Michel A., Barkema H., Kralik P., Kostoulas P., Citer L., Griffin F., Barwell R., Moreira M.A.S., Slana I., Koehler H., Singh S.V., Yoo H.S., Chávez‑Gris G., Goodridge A., Ocepek M., Garrido J., Stevenson K., Collins M., Alonso B., Cirone K., Paolicchi F., Gavey L., Rahman M.T., de Marchin E., Van Praet W., Bauman C., Fecteau G., McKenna S., Salgado M., Fernández‑Silva J., Dziedzinska R., Echeverría G., Seppänen J., Thibault V., Fridriksdottir V., Derakhshandeh A., Haghkhah M., Ruocco L., Kawaji S., Momotani E., Heuer C., Norton S., Cadmus S., Agdestein A., Kampen A., Szteyn J., Frössling J., Schwan E., Caldow G., Strain S., Carter M., Wells S., Munyeme M., Wolf R., Gurung R., Verdugo C., Fourichon C., Yamamoto T., Thapaliya S., Di Labio E., Ekgatat M., Gil A., Alesandre A.N., Piaggio J., Suanes A. & de Waard J.H. 2019. Control of paratuberculosis: who, why and how. A review of 48 countries. BMC Vet Res, 15, 198.
