A, Venn diagram of gene promoters decorated by H3K56Ac in SIRT6 WT, SIRT6 KO and SIRT6 KO PDAC cells engineered to express SIRT6 WT as determined by Chromatin immunoprecipitation (ChIP) sequencing (Seq). B, Integrative genomics viewer track of H3K56Ac levels along the Lin28b promoter of the indicated murine PDAC cell lines. C, Expression of Lin28b in four independent SIRT6 WT and SIRT6 KO murine PDAC cell lines as measured by qRTPCR; data are presented as mean ± s.e.m. between three independent experiments. D, IB of chromatin and WCL from individual SIRT6 WT and SIRT6 KO PDAC cell lines. E,F qRTPCR analysis for expression of LIN28B and SIRT6 in human PDAC cell lines displayed as a bar graph (E) and scatter plot (F) demonstrating an inverse correlation; data represent mean ± s.e.m. between three independent experiments. G, Immunohistochemistry of LIN28B and SIRT6 in human PDAC samples (left) compared to normal pancreas (right). H, I, LIN28B levels in Panc3.27 expressing empty vector, S6WT or the S6HY catalytically inactive mutant as measured by qRTPCR (H) and IB (I). J, Lin28b levels in two independent SIRT6 KO murine PDAC cells lines expressing empty vector, S6WT or S6HY. Scale bars, black 50 μm. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001. See also Fig S3.