Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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Correlation analyses of CpG island methylation of cluster of differentiation 4 protein with gene expression and T lymphocyte subpopulation traits

  • Zhao, Xueyan (Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences) ;
  • Wang, Yanping (Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences) ;
  • Guo, Jianfeng (Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences) ;
  • Wang, Jiying (Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences)
  • Received : 2017.10.31
  • Accepted : 2018.02.11
  • Published : 2018.08.01
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Abstract

Objective: Cluster of differentiation 4 protein (CD4) gene is an important immune related gene which plays a significant role in T cell development and host resistance during viral infection. Methods: In order to unravel the relationship of CpG island methylation level of CD4 gene with its gene expression and T lymphocyte subpopulation traits, we used one typical Chinese indigenous breed (Dapulian, DP) and one commercial breed (Landrace), then predicted the CpG island of CD4 gene, determined the methylation status of CpG sites by bisulfite sequencing polymerase chain reaction (BSP), and carried out the correlation analyses of methylation frequencies of CpG sites with mRNA expression and T lymphocyte subpopulation traits. Results: There was one CpG island predicted in the upstream -2 kb region and exon one of porcine CD4 gene, which located 333 bp upstream from the start site of gene and contained nine CpG sites. The correlation analysis results indicated that the methylation frequency of CpG_2 significantly correlated with CD4 mRNA expression in the DP and Landrace combined population, though it did not reach significance level in DP and Landrace separately. Additionally, 15 potential binding transcription factors (TFs) were predicted within the CpG island, and one of them (Jumonji) contained CpG_2 site, suggesting that it may influence the CD4 gene expression through the potential binding TFs. We also found methylation frequency of CpG_2 negatively correlated with T lymphocyte subpopulation traits CD4+CD8-CD3-, CD4-CD8+CD3- and CD4+/CD8+, and positively correlated with CD4-CD8+CD3+ and CD4+CD8+CD3+ (for all correlation, p<0.01) in DP and Landrace combined population. Thus, the CpG_2 was a critical methylation site for porcine CD4 gene expression and T lymphocyte subpopulation traits. Conclusion: We speculated that increased methylation frequency of CpG_2 may lead to the decreased expression of CD4, which may have some kind of influence on T lymphocyte subpopulation traits and the immunity of DP population.

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References

  1. Fabbri M, Smart C, Pardi R. T lymphocytes. Int J Biochem Cell Biol 2003;35:1004-8. https://doi.org/10.1016/S1357-2725(03)00037-2
  2. Davis CB, Littman DR. Thymocyte lineage commitment: is it instructed or stochastic? Curr Opin Immunol 1994;6:266-72. https://doi.org/10.1016/0952-7915(94)90100-7
  3. Killeen N, Davis CB, Chu K, et al. CD4 function in thymocyte differentiation and T cell activation. Philos Trans R Soc Lond B Biol Sci 1993;342(1299):25-34. https://doi.org/10.1098/rstb.1993.0131
  4. Ellmeier W, Sawada S, Dan R. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol 2003;17:523-54.
  5. Adlam M, Siu G. Hierarchical interactions control CD4 gene expression during thymocyte development. Immunity 2003;18:173-84. https://doi.org/10.1016/S1074-7613(03)00021-9
  6. Zou Y, Sunshine M, Taniuchi I, et al. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nat Genet 2001;29:332-6. https://doi.org/10.1038/ng750
  7. Xu J, Liu Y, Fu W, et al. Association of the porcine cluster of differentiation 4 gene with T lymphocyte subpopulations and its expression in immune tissues. Asian-Australas J Anim Sci 2013;26:463-9. https://doi.org/10.5713/ajas.2012.12576
  8. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293(5532):1068-70. https://doi.org/10.1126/science.1063852
  9. Ioshikhes IP, Zhang MQ. Large-scale human promoter mapping using CpG islands. Nat Genet 2000;26:61-3. https://doi.org/10.1038/79189
  10. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA 2006;103:1412-7. https://doi.org/10.1073/pnas.0510310103
  11. Wachter E, Quante T, Merusi C, et al. Synthetic CpG islands reveal DNA sequence determinants of chromatin structure. Elife 2014;3:e03397.
  12. Jursch T, Miskey C, Izsvak Z, Ivics Z. Regulation of DNA transposition by CpG methylation and chromatin structure in human cells. Mob DNA 2013;4:15. https://doi.org/10.1186/1759-8753-4-15
  13. Choy JS, Wei S, Lee JY, et al. DNA methylation increases nucleosome compaction and rigidity. J Am Chem Soc 2010;132:1782-3. https://doi.org/10.1021/ja910264z
  14. Fang J, Cheng J, Wang J, et al. Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition. Nat Commun 2016;7:11197. https://doi.org/10.1038/ncomms11197
  15. Banovich NE, Lan X, McVicker G, et al. Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels. PLoS Genet 2014;10(9):e1004663. https://doi.org/10.1371/journal.pgen.1004663
  16. Dai C, Sun L, Xia R, et al. Correlation between the methylation of the FUT1 promoter region and FUT1 expression in the duodenum of piglets from newborn to weaning. 3 Biotech 2017;7:247.
  17. Yan J, Fu H, Shen J, et al. Application of bisulfite sequencing PCR in detecting the abnormal methylation of suppressor gene of wnt signaling pathway in acute promyelocytic leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2016;24:1299-304.
  18. Luo J, Ying Y, Zhang H, et al. Down-regulation of promoter methylation level of CD4 gene after MDV infection in MD-susceptible chicken line. BMC Proc 2011;Suppl 4:S7.
  19. Wang XS, Zhang Y, He YH, et al. Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows. Genet Mol Res 2013;12:6228-39. https://doi.org/10.4238/2013.December.4.10
  20. Wang X, Ao H, Zhai L, et al. Transcriptional regulation of CD4 gene expression in porcine kidney epithelial cells by virus-like double-stranded RNA and DNA methyltransferase inhibitor. Genet Mol Res 2014;13:3346-55. https://doi.org/10.4238/2014.April.29.13
  21. Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000;13:715-25. https://doi.org/10.1016/S1074-7613(00)00070-4
  22. Lunney JK, Chen H. Genetic control of host resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection. Virus Res 2010;154:161-9. https://doi.org/10.1016/j.virusres.2010.08.004
  23. Yang H. Livestock development in China: animal production, consumption and genetic resources. J Anim Breed Genet 2013;130:249-51. https://doi.org/10.1111/jbg.12045
  24. Jiang C, Xing F, Xing J, Jiang Y, Zhou E. Different expression patterns of PRRSV mediator genes in the lung tissues of PRRSV resistant and susceptible pigs. Dev Comp Immunol 2013;39:127-31. https://doi.org/10.1016/j.dci.2012.01.003
  25. Wang HZ, Lin S, Wang YP, et al. Analyses of breeds and litter effect on routine blood traits and T-lymphocyte subpopulation traits in piglets. Chinese J Anim Vet Sci 2014;22:724-30.
  26. Wang JY, Wang YP, Guo JF, et al. Selection of reference genes and determination of cytokines and receptor mRNA expression in peripheral blood of piglets. Scientia Agricultura Sinica 2015;48:1437-44.
  27. Cartharius K, Frech K, Grote K, et al. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 2005;21:2933-42. https://doi.org/10.1093/bioinformatics/bti473
  28. Li L-C, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics 2002;18:1427-31. https://doi.org/10.1093/bioinformatics/18.11.1427
  29. Bock C, Reither S, Mikeska T, et al. BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 2005;21:4067-8. https://doi.org/10.1093/bioinformatics/bti652
  30. Nakayama T, Wiest DL, Abraham KM, et al. Decreased signaling competence as a result of receptor overexpression: overexpression of CD4 reduces its ability to activate p56lck tyrosine kinase and to regulate T-cell antigen receptor expression in immature CD4+CD8+ thymocytes. Proc Natl Acad Sci USA 1993;90:10534-8. https://doi.org/10.1073/pnas.90.22.10534
  31. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293(5532):1068-70. https://doi.org/10.1126/science.1063852
  32. Meng H, Murrelle EL, Li G. Identification of a small optimal subset of CpG sites as bio-markers from high-throughput DNA methylation profiles. BMC Bioinformatics 2008;9:457. https://doi.org/10.1186/1471-2105-9-457
  33. Bensaude E, Turner JL, Wakeley PR, et al. Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J Gen Virol 2004;85:1029-37. https://doi.org/10.1099/vir.0.19637-0
  34. Chi T H, Wan M, Zhao K, et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 2002;418:195-9. https://doi.org/10.1038/nature00876
  35. Liu KY, Comstock SS, Shunk JM, Monaco MH, Donovan SM. Natural killer cell populations and cytotoxic activity in pigs fed mother's milk, formula, or formula supplemented with bovine lactoferrin. Pediatr Res 2013;74:402-7. https://doi.org/10.1038/pr.2013.125
  36. Bennett SRM, Carbone FR, Karamalis F, et al. Induction of a $CD8^+$ cytotoxic T lymphocyte response by cross-priming requires cognate $CD4^+$ help. J Exp Med 1997;186:65-70. https://doi.org/10.1084/jem.186.1.65