Proposed model of the dual action of dietary flavones in inhibiting DNA methyltransferase and histone methyltransferase.

Abstract

<p>(A) The two major epigenetic mechanisms, DNA methylation and histone methylation, acted in concert to regulate gene transcription. The DNA double helix backbone is shown in blue and red. In DNA methylation, methyl groups are added to a cytosine that is immediately 5′ to a guanine. In general, an increase in DNA methylation leads to a decrease in gene transcription. Histone methylation is accomplished by trimethylation of histone H3 lysine 27 (H3K27me3), which is catalyzed by the enhancer of zeste homolog 2 enzyme (EZH2) resulting in gene transcriptional repression; occurring to the tails of histones (histones shown in brown, with green H3K27 marks on tails), leading to a condensed chromatin state. (B) Dietary flavones viz. Apigenin, Chrysin and Luteolin can bind to the DNA bases, dock on the catalytic pocket of DNMT and HMT to inhibit methylation resulting in relaxed chromatin, increasing the likelihood of gene transcription.</p