DNA Methylation

DNA Methylation

DNA methylation is a crucial epigenetic mark where a methyl group is added to the 5-carbon of cytosine (5mC), primarily at CpG dinucleotides. It's essential for gene silencing, genomic imprinting, and X-chromosome inactivation.

DNA Methyltransferases (DNMTs)

• DNMT1: Maintenance methyltransferase that copies methylation patterns to newly synthesized DNA during replication (with UHRF1)
• DNMT3A/3B: De novo methyltransferases that establish new methylation patterns, active in development and cell differentiation
• DNMT3L: Catalytically inactive, enhances DNMT3A/B activity

TET Enzymes and Demethylation

TET enzymes (TET1/2/3) oxidize 5mC to 5-hydroxymethylcytosine (5hmC), then to 5-formylC (5fC) and 5-carboxyC (5caC). These oxidized forms are removed by TDG and base excision repair, completing active demethylation.

CpG Islands

CpG islands are regions with high CpG density, often found at promoters. They're typically unmethylated in active genes. H3K4me3 protects CpG islands from de novo methylation by blocking DNMT3 binding.

Inheritance

DNMT1's high fidelity (~95%) ensures methylation patterns are inherited through cell divisions. Hemi-methylated CpGs after replication are recognized by UHRF1, which recruits DNMT1 to complete methylation of the daughter strand.