DNA Methylation Resource Center


Since first discovered in bacteria nearly 100 years ago, DNA methylation has been shown to be a crucial epigenetic regulator of gene expression and genomic organization in nearly all organisms. In eukaryotes, this modification of DNA is found in cytosines (C), where DNA Methyl Transferases (DNMTs) mediate the transfer of a methyl group to cytosines, converting them to 5-methylcytosine (5-mC). This minor DNA modification can change the activity of DNA without changing the primary sequence itself.

DNA methylation appears almost exclusively in the context of CpG dinucleotides. Overall, these dinucleotides are relatively rare in the mammalian genome and are mainly clustered in what are called CpG islands, ranging between 500-2,000 base pairs in length. In humans, >60% of these CpG islands are in gene promoters. While most CpG dinucleotides are methylated, those within promoter regions are almost always unmethylated and are associated with transcriptionally active genes. DNA methylation of promoters is linked with several fundamental processes including genomic imprinting, X-chromosome inactivation, and repression of transposable elements. Aberrant changes in DNA methylation patterns are associated with many diseases as well as aging.

DNA methylation is reversible. TET enzymes, a family of ten-eleven translocation (TET) methylcytosine dioxygenases are central for DNA demethylation. These enzymes convert 5-mC to 5-hmC. Their further action can catalyze the conversion of 5-hmC to 5-formylcytosine (5-fC) and then to 5-carboxycytosine (5-caC). Both 5-fC and 5-caC can then be removed from the DNA sequence by base excision repair and replaced by an unmethylated cytosine. While 5-hmC was originally believed to be an incidental mark on the way to demethylation, evidence has since shown that the Tet family of proteins and 5-hmC are in fact involved in normal development as well as many disease states. In mammals, 5-hmC is found in high levels in the brain and in other tissues of the central nervous system.

Many scientists have engaged in studies to understand the distribution of DNA methylation, leading to the emergence of numerous methods for mapping 5-mC and 5-hmC. The sheer number of options can be overwhelming and make it difficult to know where to start. However, while there are many approaches for studying DNA methylation, the best tactic can be determined based on the goals and resources for a particular experiment, with each method having advantages and drawbacks.







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