DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence, when located in a gene promoter, DNA methylation typically acts to repress gene transcription. Two of DNAs four bases, cytosine and adenine, can be methylated. 3% in Escherichia coli,0. 03% in Drosophila, adenine methylation has been observed in bacterial, plant and recently in mammalian DNA, but have received considerably less attention. In plants and other organisms, DNA methylation is found in three different sequence contexts, CG, CHG or CHH, in mammals however, DNA methylation is almost exclusively found in CpG dinucleotides, with the cytosines on both strand being usually methylated. Non-CpG methylation can however be observed in embryonic cells, and has also been indicated in neural development. Furthermore, non-CpG methylation has also observed in hematopoietic progenitor cells. The DNA methylation landscape of vertebrates is very particular compared to other organisms, in vertebrates, around 60-80% of CpG are methylated in somatic cells and DNA methylation appears as a default state that has to be specifically excluded from defined locations. High CpG methylation in mammalian genomes has an evolutionary cost because it increases the frequency of spontaneous mutations, loss of amino-groups occurs with a high frequency for cytosines, with different consequences depending on their methylation. Excluding repeated sequences, there are around 25,000 CpG islands in the human genome and they are major regulatory units and around 50% of CpG islands are located in gene promoter regions, while another 25% lie in gene bodies, often serving as alternative promoters. Reciprocally, around 60-70% of human genes have a CpG island in their promoter region, the majority of CpG islands are constitutively unmethylated and enriched for permissive chromatin modification such as H3K4 methylation. In somatic tissues, only 10% of CpG islands are methylated, DNA methylation was probably present at some extent in very early eukaryote ancestors. In virtually every organism analyzed, methylation in promoter regions correlates negatively with gene expression, cpG-dense promoters of actively transcribed genes are never methylated, but reciprocally transcriptionally silent genes do not necessarily carry a methylated promoter. DNA methylation may affect the transcription of genes in two ways and this link between DNA methylation and chromatin structure is very important. DNA methylation is a transcriptional repressor, at least in CpG dense contexts. Transcriptional repression of protein-coding genes appears essentially limited to specific classes of genes that need to be silent permanently. While DNA methylation does not have the flexibility required for the fine-tuning of gene regulation, transposon control is one the most ancient function of DNA methylation that is shared by animals, plants and multiple protists. It is even suggested that DNA methylation evolved precisely for this purpose, a function that appears even more conserved than transposon silencing is positively correlated with gene expression. In almost all species where DNA methylation is present, DNA methylation is especially enriched in the body of highly transcribed genes, the function of gene body methylation is not well understood
Representation of a DNA molecule that is methylated. The two white spheres represent methyl groups. They are bound to two cytosinenucleotide molecules that make up the DNA sequence.
Typical DNA methylation landscape in mammals
Dynamic of DNA methylation during mouse embryonic development. E3.5-E6, etc., refer to days after fertilization. PGC: primordial germ cells