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

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.

► The DNA in the Ifng promoter is hypermethylated in neonatal foals.
► The demethylation of the DNA was correlated with an increase in IFN-γ mRNA level.
► The demethylation of the DNA was correlated with age of horses.
► The demethylation was accelerated in foals with barn-air exposure.
► This demethylation may be induced by lymphoproliferation.