Regions that had the greatest difference in DNA methylation in both AREG and EREG as a result of integrin α6β4 signaling corresponded to areas enriched in H3K27Ac marks (Fig. 3A,B), as annotated by the ENCODE project, that are reported to mark active enhancer elements34. Additionally, a super-enhancer associated with AREG and EREG expression lies between AREG and the AREG pseudogene35. We found no significant differences in super-enhancer DNA methylation (data not shown), indicating that it is unlikely that DNA methylation of this element is the major driver for enhanced AREG and EREG gene expression. Taken together, these data, along with our observation that BRD4 is required for AREG and EREG expression, indicate that DNA demethylation of enhancer elements localized within the proximal promoters of AREG and EREG drive expression in response to integrin α6β4 signaling.