Background: Different diets result in significantly different phenotypes through metabolic and genomic reprogramming. Epigenetic marks, identified in humans and mouse models through caloric restriction, a high-fat diet or the intake of specific bioactives, suggest that genomic reprogramming drives this metabolic reprogramming and mediates the effect of nutrition on health. Histone modifications encode the epigenetic signal, which adapts genome functions to environmental conditions, including diets, by tuning the structure and properties of chromatin. To date, the effect of different diets on the genome-wide distribution of critical histone marks has not been determined. Methods: Using chromatin immunoprecipitation sequencing, we investigated the distribution of the trimethylation of lysine 4 of histone H3 in the liver of mice fed for one year with five different diets, including: chow containing yellow corn powder as an extra source of plant bioactives or specifically enriched with cyanidin-3-O-Glucoside, high-fat-enriched obesogenic diets, and caloric-restricted pro-longevity diets. Conclusions: Comparison of the resulting histone mark profiles revealed that functional food containing cyanidin determines a broad effect.