ABSTRACT

DNA methylation at cytosines followed by guanines, CpGs, forms one of the multiple layers of epigenetic mechanisms controlling and modulating gene expression through chromatin structure. It closely interacts with histone modifications and chromatin remodeling complexes to form the local and higher-order chromatin landscape. DNA methylation is dynamic throughout life, essential for proper mammalian development and plays a role in maintaining genomic stability. Writers and readers of DNA methylation patterns have been characterized defining the role of DNA methylation in the activation of cell-type specific gene expression programs. Additional DNA modifications such as 5-hydroxymethylcytosine have been identified in several cell types and constitute intermediates in the TET-catalyzed active demethylation process, but have also shown to have distinct gene regulatory roles. Changes of DNA methylation levels and patterns have been reported in many complex diseases, especially cancer, where DNA methylation is now used as biomarkers for early detection and response to treatment.