Gene regulatory mechanisms downstream of DNA methylation

Cytosine DNA methylation is a conserved epigenetic modification that regulates gene expression, represses transposable elements and maintains genome stability across diverse eukaryotes. Although major advances have uncovered the pathways involved in the establishment, maintenance and removal of DNA methylation, the downstream mechanisms by which this mark influences transcriptional programmes and shapes chromatin structure are less well understood. Here, we review how specialized reader proteins and transcription factors interpret DNA methylation to preserve methylation patterns, recruit effector complexes, regulate chromatin accessibility and interact with parallel epigenetic systems to mediate transcriptional silencing and activation across mammals and plants. We highlight that robust transcriptional and epigenetic states emerge from overlapping, layered and partially redundant DNA methylation-dependent mechanisms. Together, these insights provide a framework for understanding how DNA methylation shapes the epigenome to regulate development, differentiation and disease progression.