Caffeic acid phenethyl ester, a coffee polyphenol, inhibits DNA methylation in vitro and in vivo

DNA methylation represents an important epigenetic regulation of the genome. Earlier studies have suggested that dietary phenolic compounds including those contained in coffee, tea and soy products may modulate the level of DNA methylation. In this study, we first characterize the effect of caffeic acid phenethyl ester (CAPE) and other dietary phenolic compounds on DNA methylation in vitro. The IC₅₀ values of CAPE, daidzein, isorhamnetin and genistein are 7.6, 6.9, 6.2, and 4.3 μM, respectively, in an in-vitro enzymatic assay system. Computational analysis indicates that CAPE, daidzein, isorhamnetin and genistein can bind inside the DNA substrate-binding site in human DNMT1 with a favorable binding energy. In an animal study, we find that maternal CAPE treatment shifts the coat color distribution of the 21-day-old A^vy/a offspring towards the yellow phenotype, indicating that CAPE inhibits the methylation of the agouti gene promoter sequence in vivo. The results from this study may shed light on the potential epigenetic effect in the offspring resulting from maternal intake of certain coffee phenolics during pregnancy.