Rajabi, HasanTagde, AshujitAlam, MaroofBouillez, AudreyPitroda, SeanSuzuki, YozoKufe, Donald2016-12-022016Rajabi, Hasan, Ashujit Tagde, Maroof Alam, Audrey Bouillez, Sean Pitroda, Yozo Suzuki, and Donald Kufe. 2016. “DNA METHYLATION BY DNMT1 AND DNMT3b METHYLTRANSFERASES IS DRIVEN BY THE MUC1-C ONCOPROTEIN IN HUMAN CARCINOMA CELLS.” Oncogene :10.1038/onc.2016.180. doi:10.1038/onc.2016.180. http://dx.doi.org/10.1038/onc.2016.180.0950-9232http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626079Aberrant expression of the DNA methyltransferases (DNMTs) and disruption of DNA methylation patterns are associated with carcinogenesis and cancer cell survival. The oncogenic MUC1-C protein is aberrantly overexpressed in diverse carcinomas; however, there is no known link between MUC1-C and DNA methylation. Our results demonstrate that MUC1-C induces expression of DNMT1 and DNMT3b, but not DNMT3a, in breast and other carcinoma cell types. We show that MUC1-C occupies the DNMT1 and DNMT3b promoters in complexes with NF-κB p65 and drives DNMT1 and DNMT3b transcription. In this way, MUC1-C controls global DNA methylation as determined by analysis of LINE-1 repeat elements. The results further demonstrate that targeting MUC1-C downregulates DNA methylation of the CDH1 tumor suppressor gene in association with induction of E-cadherin expression. These findings provide compelling evidence that MUC1-C is of functional importance to induction of DNMT1 and DNMT3b and, in turn, changes in DNA methylation patterns in cancer cells.en-USMUC1-CDNMT1DNMT3bDNA methylationE-cadherinepigenetic regulationJournal Article2016-12-0210.1038/onc.2016.180