Fig. 1

Epigenetic modifications of pathologic genes associated with DKD. In diabetic conditions, a series of epigenetic modifications occurred in protective genes, inflammatory and fibrotic genes, or even ncRNAs contribute to renal damage. In the formation of active chromatin, H3K4me1/2/3 mediated by histone methyltransferases such as SET7/9 and H3K9/14ac, H3K18/23/27ac, and H4K5/8/14ac mediated by histone acetyl transferases such as p300, WDR5, and PCAF are involved. In the contrary, H3K9me2/3 and H3K27me3 mediated by HMTs EZH2 and SUV39H1, respectively, and histone PTMs mediated by HDACs Sirt6 and HDAC9 play repressive role on the transcription of protective genes. DNA methylation mediated by DNA methyltransferases is also associated with transcriptional repression. Under disease state such as diabetes and renal injury, epigenetic alterations can also lead to the dysregulation of ncRNAs, which take part in persistent epigenetic alterations. Epigenetic modifications of pathologic genes associated with DKD play key roles in metabolic memory. HATs: histone acetyl transferases; HMTs, histone lysine methyltransferase; HDACs: histone deacetylase; PTMs, post-translational modifications