TET1-mediated different transcriptional regulation in prostate cancer

The recent studies demonstrated that the global 5-hydroxymethylcytosine (5 hmC) level decreased in prostate cancer (PCa) involved the 5-methylcytosine (5 mC) hydroxymethylase, Ten-eleven translocation (TET)1 reduction. 5 hmC and TET1 were both revealed a dual function in bivalent domain associated with developmental regulators in embryonic stem cell model. However, the mechanism underlying the DNA methylation and hydroxymethylation change mediated by TET1 downregulation in PCa remains unclear. Herein, using BSP to assess the 5 mC level in promoters of ten specific marker gene in PCa, our results present that Cdh1, Gstp1, Pten, Apc, Runx3 and Mgmt are observed to be hypermethylated in promoters and lower expression while Cyr61, Sema3c and Ptgs2 are reversed patterns compared to the normal prostate tissues. Furthermore, using ChIP methods to investigate the H3K4me3 and H3K27me3 patterns in promoters, these four markers are all demonstrated to be associated with Polycomb-repressed characterization and upregulated in response to TET1/PRC2 reduction in PCa. Thus, our findings reveal a distinct activating and repressive function of TET1-mediated transcriptional regulation in prostate cancer.