Figure 3. Schematic model showing SIRT6-depdendent transcriptional regulation of IGF/Akt signaling-related genes.
Under basal conditions SIRT6 binds to chromatin as a complex with c-jun and deacetylates histones (H3K9), leading to chromatin condensation and repression of the IGF/Akt signaling-related genes. Under pathological stress, SIRT6 levels are reduced leading to increased acetylation of H3K9 at the promoters of IGF/Akt signaling related genes and c-jun mediated transcriptional activation. IGF/Akt signaling related genes which are activated in SIRT6KO hearts are shown on the right side of the figure (For details see ref 34).