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Developmental and comparative immunology2012; 39(3); 273-278; doi: 10.1016/j.dci.2012.09.006

The promoter region of interferon-gamma is hypermethylated in neonatal foals and its demethylation is associated with increased gene expression.

Abstract: While born with a limited production, foals' interferon-gamma (IFN-γ) expression increases after birth. The underlying mechanisms remain unknown. DNA methylation is considered to be involved. Therefore, the DNA methylation status of the Ifng promoter in CD4(+) cells from neonatal foal was determined using a methylation-specific PCR (MSP), and its relevance to IFN-γ mRNA expression was estimated. The effect of environment on the DNA methylation was also evaluated by comparing ponies that were kept in a barn versus those on pasture. The DNA in the Ifng promoter was hypermethylated and its demethylation was correlated with an increase in IFN-γ mRNA expression and age. This age-associated demethylation was accelerated by barn-air exposure. In conclusion, IFN-γ expression in foals appears to be controlled by DNA methylation in the promoter region of Ifng. The age-associated demethylation of the DNA in foals may be induced by exposure to environmental antigens and their effect on lymphoproliferation.
Publication Date: 2012-10-11 PubMed ID: 23063468DOI: 10.1016/j.dci.2012.09.006Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

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The researchers focused on the gene expression of interferon-gamma (IFN-γ) in neonatal foals. They found that environmental factors, such as barn-air exposure, and the animal’s age influenced the methylation status of the promoter region of this gene and subsequently its expression levels.

Understanding Interferon-gamma and DNA Methylation

  • The study is centered on the gene expression of Interferon-gamma (IFN-γ), a type of protein in neonatal foals, which are young horses. Though newborn foals have limited production of IFN-γ, its expression increases after birth.
  • DNA methylation is involved in the regulation of gene expression. In this context, it’s important to note that methylation is when a methyl group is added to a DNA molecule. When this happens to the promoter region, it can inhibit gene expression. Hence, methylation is an important aspect in gene regulation and cellular differentiation.
  • Methylation of Interferon-gamma in Foals

    • The researchers analyzed the methylation status of the Ifng promoter in the CD4(+) cells from the neonatal foal. They did this using a method called methylation-specific PCR (MSP). The Ifng promoter region refers to the sequence of DNA that initiates transcription of the Ifng gene.
    • Results found that the DNA in the Ifng promoter was hypermethylated in the foals. Hypermethylation usually leads to the silencing of gene expression. This hypermethylation was found to decrease as the foal grew older.
    • Environmental Influence and Implications

      • Interestingly, the rate of this age-associated demethylation was found to speed up when the foals were exposed to barn-air. This gave researchers an understanding that exposure to certain environmental factors could potentially accelerate the demethylation process.
      • The effect of DNA methylation and demethylation on the gene expression of IFN-γ suggests that this could be a mechanism controlling the IFN-γ expression in foals.
      • The researchers conclude that the age-associated demethylation of the DNA in foals may be induced by exposure to environmental factors. This opens new considerations for how environmental antigens might impact lymphoproliferation, the rapid production of lymphocytes, a type of white blood cell that plays an important role in the body’s immune response.

Cite This Article

APA
Sun L, Gong Z, Oberst EJ, Betancourt A, Adams AA, Horohov DW. (2012). The promoter region of interferon-gamma is hypermethylated in neonatal foals and its demethylation is associated with increased gene expression. Dev Comp Immunol, 39(3), 273-278. https://doi.org/10.1016/j.dci.2012.09.006

Publication

ISSN: 1879-0089
NlmUniqueID: 7708205
Country: United States
Language: English
Volume: 39
Issue: 3
Pages: 273-278
PII: S0145-305X(12)00211-X

Researcher Affiliations

Sun, Lingshuang
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, USA.
Gong, Zhangbin
    Oberst, Eric J
      Betancourt, Alejandra
        Adams, Amanda A
          Horohov, David W

            MeSH Terms

            • Age Factors
            • Animals
            • Animals, Newborn
            • CD4-Positive T-Lymphocytes / immunology
            • Cell Proliferation
            • Cell Separation
            • Cells, Cultured
            • DNA Methylation
            • Environmental Exposure / adverse effects
            • Flow Cytometry
            • Gene Expression Regulation
            • Horses / genetics
            • Horses / immunology
            • Interferon-gamma / genetics
            • Promoter Regions, Genetic / genetics

            Citations

            This article has been cited 4 times.
            1. Ząbek T, Semik-Gurgul E, Szmatoła T, Gurgul A, Fornal A, Bugno-Poniewierska M. Methylation Marks of Blood Leukocytes of Native Hucul Mares Differentiated in Age. Int J Genomics 2019;2019:2839614.
              doi: 10.1155/2019/2839614pubmed: 31281827google scholar: lookup
            2. Green BB, McKay SD, Kerr DE. Age dependent changes in the LPS induced transcriptome of bovine dermal fibroblasts occurs without major changes in the methylome. BMC Genomics 2015 Jan 27;16(1):30.
              doi: 10.1186/s12864-015-1223-zpubmed: 25623529google scholar: lookup
            3. Ząbek T, Semik E, Wnuk M, Fornal A, Gurgul A, Bugno-Poniewierska M. Epigenetic structure and the role of polymorphism in the shaping of DNA methylation patterns of equine OAS1 locus. J Appl Genet 2015 May;56(2):231-8.
              doi: 10.1007/s13353-014-0244-7pubmed: 25195205google scholar: lookup
            4. Lovinsky-Desir S, Ridder R, Torrone D, Maher C, Narula S, Scheuerman M, Merle D, Kattan M, DiMango E, Miller RL. DNA methylation of the allergy regulatory gene interferon gamma varies by age, sex, and tissue type in asthmatics. Clin Epigenetics 2014;6(1):9.
              doi: 10.1186/1868-7083-6-9pubmed: 24891923google scholar: lookup