ARTICLE 74 FEED & ADDITIVE MAGAZINE May 2025 methylation heavily depends on methyl groups provided primarily by dietary methionine, choline, and folate. The enzyme DNA methyltransferase (DNMT) transfers these methyl groups onto cytosines at CpG sites, critically regulating gene expression. Dairy nutritionists typically supplement methionine and choline following NASEM (2021) recommendations, often unaware of their epigenetic effects. Meeting these nutrient guidelines enhances DNA methylation, suppresses pro-inflammatory cytokines, strengthens immune responses, and reduces susceptibility to diseases such as mastitis and metritis. Conversely, nutrient deficiencies disrupt methylation patterns, increasing inflammation and disease risk. Histone modifications mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) similarly rely on nutrients. Histone acetylation enhances gene expression, dependent on acetyl-CoA, linking energy metabolism directly to gene regulation (Figure 2). EPIGENETIC EFFECTS ON IMMUNITY, HEALTH, AND LONGEVITY Emerging research highlights epigenetics’ significant impact on immunity and health. Proper nutrient intake activates protective immune pathways, enhancing pathogen resistance and reducing chronic inflammation. Selenium, for instance, modulates epigenetic pathways governing selenoprotein expression, essential for a stronger immunity and antioxidant protection. Short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate—produced via ruminal fiber fermentation—also influence epigenetics. Butyrate strongly inhibits HDACs, promoting anti-inflammatory expression, while acetate and propionate indirectly enhance histone acetylation by supplying acetyl groups. These SCFAs significantly impact gut health, systemic immunity, and overall animal health (Kasubuchi et al., 2015). Epigenetic activation begins within the first few days of life. Calves receiving insufficient colostrum or nutritional restriction during critical developmental periods typically underperform later in life. Colostrum provides essential nutrients and bioactive factors for positive epigenetic programming. Inadequate colostrum intake or early-life nutritional deficiencies can alter DNA methylation, histone modifications, and gene expression, impairing metabolism and immunity, increasing susceptibility to disease, and adversely affecting adult productivity. Epigenetic Mechanisms Chromatin Histone Tail Histone Methyl Group Gene Gene DNA Chromosome Epigenetic Factor DNA Accessible, Gene Active DNA Inaccesible, Gene Inactive Figure 1 Methionine Choline Folic acid Vitamin B12 Zinc Selenium DNA methyltransferase (DNMT) CpG site CH3 CH3 CH3 DNA methylation Gene expression Role of Nutrients in Epigenetic Regulation through DNA Methylation Figure 2
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