Epigenetic mechanisms, particularly DNA methylation, play a pivotal role in the regulation of gene expression without altering the underlying DNA sequence. Despite the vast array of research, the intricate details of these processes in mammalian cells remain not fully elucidated. The objective of this study was to investigate the patterns and functions of DNA methylation in the regulation of gene expression in mammalian cells. We employed whole-genome bisulfite sequencing and RNA-seq to map methylation landscapes and correlate these with expression profiles in mammalian cell lines. Our findings reveal that specific methylation sites are crucial for the repression of certain gene clusters involved in cell differentiation and proliferation. Moreover, the study highlights the dynamic nature of methylation patterns during cellular stress responses, suggesting potential therapeutic targets for epigenetic drugs in cancer treatment. In conclusion, this research provides significant insights into the complexity of epigenetic regulation via DNA methylation, contributing to the broader understanding of its implications in health and disease.