Post-translational modifications, such as lysine methylation regulated by HMTs and KDMs, or histone acetylation regulated by HATs or HDACs on the N-terminal histone tails of chromatin, play important roles in regulating gene expression. In the proposed model, under normal conditions, various chromatin modifiers mediate sufficient levels of repressive histone marks to maintain strict control of pathologic gene expression. However, under diabetic conditions, such as hyperglycemia, the negative regulators may be lost while positive regulators or activating histone marks may be increased, thus leading to relaxing or opening of the chromatin structure around these genes to increase their transcription. Various histone modifications could be involved. Ac: Acetylation; HAT: Histone acetyltransferase; HDAC: Histone deacetylase; HMT: Histone methyltransferase; KDM: Histone demethylase; me: Methylation.