Schematic representation of the proposed effect of hyperhomocysteinemia on DNA methylation and atherosclerosis. SAH indicates S-adenosyl-homocysteine; DNMT, DNA methyltransferase. Hcy may induce the accumulation of SAH, a potent inhibitor of cellular methylation, as well as subsequent cellular hypomethylation, including DNA hypomethylation. Hcy-induced DNA demethylation is mediated by DNMT1 inactivation, which leads to demethylation of the cyclin A promoter CDE, and also leads to cyclin A promoter remodeling. Cyclin A chromatin remodeling may facilitate the function of CDE suppressor and result in cyclin A suppression. The activity of the suppressor element is increased due to DNA hypomethylation, which promotes chromatin remodeling and the access of suppressors to the chromatin, leading to transcriptional inhibition.