Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes with Susceptibility to Bovine Staphylococcus Aureus Subclinical Mastitis

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 15

PMID 27411928

Citations 31

Authors

Minyan Song

Yanghua He

Huangkai Zhou

Yi Zhang

Xizhi Li

Ying Yu

Affiliations

Soon will be listed here.

Abstract

Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome-wide integrative analysis of DNA methylation and transcriptional expression to identify candidate genes and pathways relevant to bovine S. aureus subclinical mastitis. The genome-scale DNA methylation profiles of peripheral blood lymphocytes in cows with S. aureus subclinical mastitis (SA group) and healthy controls (CK) were generated by methylated DNA immunoprecipitation combined with microarrays. We identified 1078 differentially methylated genes in SA cows compared with the controls. By integrating DNA methylation and transcriptome data, 58 differentially methylated genes were shared with differently expressed genes, in which 20.7% distinctly hypermethylated genes showed down-regulated expression in SA versus CK, whereas 14.3% dramatically hypomethylated genes showed up-regulated expression. Integrated pathway analysis suggested that these genes were related to inflammation, ErbB signalling pathway and mismatch repair. Further functional analysis revealed that three genes, NRG1, MST1 and NAT9, were strongly correlated with the progression of S. aureus subclinical mastitis and could be used as powerful biomarkers for the improvement of bovine mastitis resistance. Our studies lay the groundwork for epigenetic modification and mechanistic studies on susceptibility of bovine mastitis.

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References

Ibeagha-Awemu E, Ibeagha A, Messier S, Zhao X . Proteomics, genomics, and pathway analyses of Escherichia coli and Staphylococcus aureus infected milk whey reveal molecular pathways and networks involved in mastitis. J Proteome Res. 2010; 9(9):4604-19. DOI: 10.1021/pr100336e. View

Bobetsis Y, Barros S, Lin D, Weidman J, Dolinoy D, Jirtle R . Bacterial infection promotes DNA hypermethylation. J Dent Res. 2007; 86(2):169-74. DOI: 10.1177/154405910708600212. View

Wang D, Wang Z, Yan Z, Wu J, Ali T, Li J . Bovine mastitis Staphylococcus aureus: antibiotic susceptibility profile, resistance genes and molecular typing of methicillin-resistant and methicillin-sensitive strains in China. Infect Genet Evol. 2015; 31:9-16. DOI: 10.1016/j.meegid.2014.12.039. View

Ball M, Li J, Gao Y, Lee J, LeProust E, Park I . Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009; 27(4):361-8. PMC: 3566772. DOI: 10.1038/nbt.1533. View

Jensen K, Gunther J, Talbot R, Petzl W, Zerbe H, Schuberth H . Escherichia coli- and Staphylococcus aureus-induced mastitis differentially modulate transcriptional responses in neighbouring uninfected bovine mammary gland quarters. BMC Genomics. 2013; 14:36. PMC: 3598231. DOI: 10.1186/1471-2164-14-36. View

Halasa T, Huijps K, Osteras O, Hogeveen H . Economic effects of bovine mastitis and mastitis management: a review. Vet Q. 2007; 29(1):18-31. DOI: 10.1080/01652176.2007.9695224. View

Shook G, Schutz M . Selection on somatic cell score to improve resistance to mastitis in the United States. J Dairy Sci. 1994; 77(2):648-58. DOI: 10.3168/jds.S0022-0302(94)76995-2. View

Li L, Dahiya R . MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002; 18(11):1427-31. DOI: 10.1093/bioinformatics/18.11.1427. View

Almeida R, Matthews K, Cifrian E, Guidry A, Oliver S . Staphylococcus aureus invasion of bovine mammary epithelial cells. J Dairy Sci. 1996; 79(6):1021-6. DOI: 10.3168/jds.S0022-0302(96)76454-8. View

10.

Zhang X, Lv C, Liu X, Hao D, Qin J, Tian H . Genome‑wide analysis of DNA methylation in rat lungs with lipopolysaccharide‑induced acute lung injury. Mol Med Rep. 2013; 7(5):1417-24. DOI: 10.3892/mmr.2013.1405. View

11.

Schmidt T, Kock M, Ehlers M . Diversity and antimicrobial susceptibility profiling of staphylococci isolated from bovine mastitis cases and close human contacts. J Dairy Sci. 2015; 98(9):6256-69. DOI: 10.3168/jds.2015-9715. View

12.

Wang X, Zhang Y, He Y, Ma P, Fan L, Wang Y . Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows. Genet Mol Res. 2013; 12(4):6228-39. DOI: 10.4238/2013.December.4.10. View

13.

Eckhardt F, Lewin J, Cortese R, Rakyan V, Attwood J, Burger M . DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 2006; 38(12):1378-85. PMC: 3082778. DOI: 10.1038/ng1909. View

14.

Tao W, Mallard B . Differentially expressed genes associated with Staphylococcus aureus mastitis of Canadian Holstein cows. Vet Immunol Immunopathol. 2007; 120(3-4):201-11. DOI: 10.1016/j.vetimm.2007.06.019. View

15.

Dufour S, Dohoo I, Barkema H, DesCoteaux L, DeVries T, Reyher K . Manageable risk factors associated with the lactational incidence, elimination, and prevalence of Staphylococcus aureus intramammary infections in dairy cows. J Dairy Sci. 2012; 95(3):1283-300. DOI: 10.3168/jds.2011-4711. View

16.

Li Q, Hu X, Li J, Du Z, Chen L, Yin G . Genome-wide mapping of DNA methylation in chicken. PLoS One. 2011; 6(5):e19428. PMC: 3088676. DOI: 10.1371/journal.pone.0019428. View

17.

Gillet Y, Issartel B, Vanhems P, Fournet J, Lina G, Bes M . Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002; 359(9308):753-9. DOI: 10.1016/S0140-6736(02)07877-7. View

18.

Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D . Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res. 2007; 67(3):876-80. DOI: 10.1158/0008-5472.CAN-06-2995. View

19.

Siegfried Z, Eden S, Mendelsohn M, Feng X, Tsuberi B, Cedar H . DNA methylation represses transcription in vivo. Nat Genet. 1999; 22(2):203-6. DOI: 10.1038/9727. View

20.

Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong C . Dynamic changes in the human methylome during differentiation. Genome Res. 2010; 20(3):320-31. PMC: 2840979. DOI: 10.1101/gr.101907.109. View