Epigenetic Regulation of Antioxidant Gene Expression in Zebu Cattle Adapted to Trypanosome Tolerance in Adamawa State, North East Nigeria

Zebu cattle in the tsetse-endemic belt of Adamawa State, North East Nigeria, demonstrate a spectrum of trypanotolerance that is not fully explained by genetic polymorphisms, raising the hypothesis that epigenetic regulation of antioxidant gene networks may contribute to this phenotypic variation. This doctoral study investigated DNA methylation and histone acetylation patterns at promoter regions of key antioxidant genes including nuclear factor erythroid 2-related factor 2, superoxide dismutase 1, and heme oxygenase-1 in tolerant versus susceptible Zebu cattle during experimental Trypanosoma brucei brucei infection in Adamawa State. Forty cattle classified as tolerant based on sustained haemoglobin above 8 g/dL and forty susceptible cattle matched for age and sex were enrolled. Genome-wide DNA methylation was assessed by reduced representation bisulphite sequencing, and histone acetylation by chromatin immunoprecipitation followed by quantitative PCR. Nuclear factor erythroid 2-related factor 2 promoter regions were significantly hypomethylated in tolerant cattle compared to susceptible animals, correlating with higher nuclear factor erythroid 2-related factor 2 messenger RNA and protein expression and greater downstream antioxidant enzyme activities. Histone H3 lysine 27 acetylation was enriched at superoxide dismutase 1 and heme oxygenase-1 gene bodies in tolerant cattle. These original epigenetic findings provide a novel mechanistic contribution to understanding trypanotolerance in Nigerian Zebu and establish the epigenetic antioxidant axis as a target for selective breeding and pharmaceutical enhancement of host resistance in North East Nigeria. Keywords: epigenetics, trypanotolerance, nuclear factor erythroid 2-related factor 2, antioxidant genes, Zebu cattle.