In previous work, we identified a differential DNA methylation profile between left (L) and right (R) breast tumors. L tumors exhibited enhanced membrane depolarization, increased proliferation, and elevated stemness scores. Given the inherent asymmetry of L-R mammary glands, it is reasonable to expect bioelectric and epigenetic differences, both responsive to environmental modulation. One key question we are exploring now is whether bioelectricity and epigenetics form a dual circuit. In this work, we present our latest findings addressing this question. Through in-silico analyses, we found increased expression of DNA methylation writers in L tumors (Welch’s unpaired t-test, p=0,004). To investigate potential global methylation differences between L-R tumors, we examined RRBS data from three paired L-R xenograft tumors. Additionally, we used R-TCGA BioLinks to analyze the complete methylation of 350,000 CpG sites. We also conducted MS-MLPA methylation analyses on cells cultured in L-R conditioned medium, targeting 20 CpG sites of imprinted regions. All approaches revealed no significant differences between L-R tumors (Wilcoxon test and paired T-test, p>0,05). We also examined methylation differences in specific ICH but found no strong correlations with laterality, leading us to conclude there are no enzymatic activity differences, despite the increased expression in L tumors. However, when MDA-MB231 cells were cultured in L-R conditioned medium, the bioelectric difference was abolished upon treatment with DNMT inhibitors. Specifically, the R-treated cells shifted from a hyperpolarized to a depolarized state, whereas the L-treated cells showed no response. These observations strongly suggest that bioelectric differences depend on DNA methylation writers, although not on their expression nor activity level. The underlying mechanisms are currently under investigation in our group, using animal models, cell culture models, and bioinformatics approaches.