Inter-Individual Variation in DNA Methylation Patterns across Two Tissues and Leukocytes in Mature Brahman Cattle

SIMPLE SUMMARY: Epigenetic modifications such as DNA methylation can influence gene expression and phenotype. Variation in DNA methylation patterns between individuals may contribute to phenotypic variation. The object of this study was to quantify the inter-individual variation in DNA methylation patterns of the anterior pituitary, amygdala and leukocytes harvested from two groups of Brahman females, one prenatally stressed and one control. There was little overlap between the sites and areas that exhibited high inter-individual variation between the two groups. The interaction between the prenatal environment and cow genotype could be responsible for the differences in location of the variation. The variation also appeared to be tissue specific, providing support for DNA methylation’s role in tissue specific gene expression. Genes that displayed high variation in methylation are active in biological pathways important to immune response, hormone production and behavior. This was the first characterization of the inter-individual variation of DNA methylation in somatic cells of beef cattle. Further research characterizing how methylated regions interact with gene expression and the environment may give useful insight into how cow performance is affected. ABSTRACT: Quantifying the natural inter-individual variation in DNA methylation patterns is important for identifying its contribution to phenotypic variation, but also for understanding how the environment affects variability, and for incorporation into statistical analyses. The inter-individual variation in DNA methylation patterns in female cattle and the effect that a prenatal stressor has on such variability have yet to be quantified. Thus, the objective of this study was to utilize methylation data from mature Brahman females to quantify the inter-individual variation in DNA methylation. Pregnant Brahman cows were transported for 2 h durations at days 60 ± 5; 80 ± 5; 100 ± 5; 120 ± 5; and 140 ± 5 of gestation. A non-transport group was maintained as a control. Leukocytes, amygdala, and anterior pituitary glands were harvested from eight cows born from the non-transport group (Control) and six from the transport group (PNS) at 5 years of age. The DNA harvested from the anterior pituitary contained the greatest variability in DNA methylation of cytosine-phosphate-guanine (mCpG) sites from both the PNS and Control groups, and the amygdala had the least. Numerous variable mCpG sites were associated with retrotransposable elements and highly repetitive regions of the genome. Some of the genomic features that had high variation in DNA methylation are involved in immune responses, signaling, responses to stimuli, and metabolic processes. The small overlap of highly variable CpG sites and features between tissues and leukocytes supports the role of variable DNA methylation in regulating tissue-specific gene expression. Many of the CpG sites that exhibited high variability in DNA methylation were common between the PNS and Control groups within a tissue, but there was little overlap in genomic features with high variability. The interaction between the prenatal environment and the genome could be responsible for the differences in location of the variable DNA methylation.