6methylcytosine

6-methylcytosine (6mC) is a DNA base modification in which a methyl group is added to the carbon-6 position of cytosine. It is chemically distinct from the more common 5-methylcytosine (5mC) and represents a separate class of cytosine methylation found in some organisms.

6mC has been detected in certain bacterial genomes and in a limited number of eukaryotic species. Its genomic abundance is typically low compared with 5mC and is unevenly distributed, sometimes enriched at specific sequence contexts or loci. In bacteria, 6mC is often associated with restriction-modification systems and may contribute to host defense; in eukaryotes, functional data are scarce, and distribution appears highly variable across lineages.

Biosynthesis and enzymes: 6mC is introduced by cytosine-6 DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the C6 position of cytosine in DNA. Enzyme specificity and occurrence vary among species.

Detection and mapping: Historically, 6mC was identified by chromatographic methods such as HPLC or mass spectrometry. High-throughput sequencing methods for 6mC are less established than those for other cytosine modifications, and mapping often relies on a combination of chemical, enzymatic, and sensitive detection techniques.

Function and significance: Proposed roles for 6mC include protection against restriction enzymes in bacteria and potential regulatory effects on gene expression or replication in some organisms. Compared with 5mC, 6mC is less well characterized, and knowledge about its erasure by cellular enzymes is limited; research in this area is ongoing.

History and overview: The modification was described in bacterial DNA in the late 20th century and has since been reported in other organisms, although its distribution and biological importance remain active topics of study.