Next, we examined the genome wide effects of integrin α6β4 on DNA methylation using our WGBS data. A total of 236,371 differentially methylated loci (DML; 207,168 hypomethylated and 29,203 hypermethylated) were identified comparing Panc1-3D7 vs. Panc1-2G6. Figure 3D illustrates the percentage of hypermethylated and hypomethylated events per chromosome as a percent of the number of DMLs. Of the DMLs identified, 87.6% were hypomethylated and 12.4% were hypermethylated, thus indicating that the integrin α6β4 shifts chromatin to a more hypomethylated state. Further analysis of these data revealed that only 3.1% of these loci were located in promoter regions, 2.1% in exonic regions, 31.1% in intronic regions and 63.1% were in intergenic regions (Fig. 3F). 13,889 differentially methylated regions (DMRs) were identified, of which only about 4% were located in CpG islands, and 5% in CpG shores (Fig. 3G). We found that 40,609 DMLs associated with H3K27Ac marks were hypomethylated as opposed to 13,679 DMLs hypermethylated. These events correspond to 4993 genes that have alterations in methylation within enhancer elements. As seen in Fig. 3H, the majority of these altered DML are localized to intronic and intergenic regions (defined in Fig. 3E) of which the majority are hypomethylated (Fig. 3K). This observation is typical of enhancer elements, as many enhancers are part of non-coding regions of the genome36. Additionally, we found that DMLs and DMRs occur predominantly within the first ten thousand base pairs on either side of the TSS with slightly more occurring after the TSS, as expected (Fig. 2I,J).