By binding to their promoters and deacetylating H3K9 at these sites, Sirt6 reduced the expression of Notch1 and Notch4, which was in consistent with the results showing that the levels of Notch1 and Notch4 were significantly increased in podocytes from Cre+/Sirt6fl/fl mice with DN or ADR nephropathy. This evidence concerns the gene NOTCH4 and liver dysplastic nodule.