Genomic patterns and context specific interpretation of DNA methylation

Methylation of CpG dinucleotides is a reversible modification of DNA that is highly prevalent throughout mammalian genomes. Recent advances generated genomic DNA methylation maps during cellular differentiation at unprecedented resolution. Combined with functional assays this revealed that dynamics in DNA methylation coincide with changes in regulatory activity and that transcription factors play an important role in shaping methylation patterns. This tightly links DNA methylation with underlying DNA sequence features and suggests that a substantial fraction of methylation changes occur downstream of gene regulation. Here we discuss our current understanding of the context-dependent readout of DNA methylation and criteria that need to be fulfilled for this modification to be instructive for gene regulation.