MTases can be divided into three different groups on the basis of the chemical reactions they catalyze: m6A and m4C methyltransferases are found primarily in prokaryotes (although recent evidence has suggested that m6A is abundant in eukaryotes[1]).

The type I restriction and modification system is composed of three polypeptides R, M and S. The M (hsdM) and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence.

In the presence of the R subunit, the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site.

When the target site is hemimethylated, the complex acts as a maintenance methyltransferase, modifying the DNA so that both strands become methylated.

[7] Among the m6A methyltransferases (N-6 adenine-specific DNA methylase) there is a group of orphan MTases that do not participate in the bacterial restriction/methylation system.

More recently, CamA from Clostridioides difficile, was shown to play key functional roles in sporulation, biofilm formations and host-adaptation.

In bacteria, these enzymes are a component of restriction-modification systems and serve as valuable tools for the manipulation of DNA.

[16] Highly conserved DNA methyltransferases of the m4C, m5C, and m6A types have been reported,[17] which appear as promising targets for the development of novel epigenetic inhibitors to fight bacterial virulence, antibiotic resistance, among other biomedical applications.

De novo methyltransferases are also active when a signal-responsive cell, such as a neuron, needs to alter protein expression.

These work throughout the life of the organism to maintain the methylation pattern that had been established by the de novo methyltransferases.

DNMT3L[26] is a protein closely related to DNMT3a and DNMT3b in structure and critical for DNA methylation, but appears to be inactive on its own.

[28] In human cancer cells DNMT1 is responsible for both de novo and maintenance methylation of tumor suppressor genes.

[citation needed] DNMT1 null mutant embryonic stem cells were viable and contained a small percentage of methylated DNA and methyltransferase activity.

Work with DNMT3a2, in neurons, found that the DNA methylation changes caused by DNMT3a2 predominantly occur in intergenic and intronic regions.

These intergenic and intronic DNA methylations were thought to likely regulate enhancer activity, alternative splicing or the expression of non-coding RNAs.

[19] Bayraktar and Kreutz[39] found that DNMT inhibitors, applied in the brain, prevented long-term memories from forming.

DNMT3L contains DNA methyltransferase motifs and is required for establishing maternal genomic imprints, despite being catalytically inactive.