DNA Methyltransferase Controls Stem Cell Aging by Regulating BMI1 and EZH2 through MicroRNAs (original) (raw)
Figure 8
Schematic diagram describing the relationship between miRNAs, PcGs, p16 and p21 and how transcriptional regulation of miRNAs, p16INK4A and p21CIP1/WAF1 occurs in DNMT inhibitor-mediated senescent MSCs.
(a) DNMT inhibition increases p16INK4A and p21CIP1/WAF1 expression directly through DNA demethylation, indirectly through an unknown pathway and, over time, induces cellular senescence. The regulation of miRNAs, which target PcG proteins, is one of the indirect pathways that increase p16INK4A and p21CIP1/WAF1 expression. (b) DNMT inhibition induces CpG island demethylation, increases active histone forms and decreases inactive histone forms in the promoter region of CDK inhibitors and in the proximity of miRNAs in hUCB-MSCs. Pri-miRNA refers to primary-miRNA.