Patterns of DNA methylation are laid out during early embryogenesis via the interplay of at least three active DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B, and targeted deletions of these genes in the mouse have demonstrated that the enzymes are essential for normal development.

DNMT1 associates with the DNA replication fork and functions as a hemi-methylase responsible for maintaining correct methylation patterns on DNA replication. DNMT3s (DNMT3A and DNMT3B) are instead de novo methyltransferases important for establishing methylation patterns during embryogenesis, and they associate with the replication fork in late S-phase during the replication of constitutive heterochromatin.

Pathology

 mutations in the DNA methyltransferase 3B (DNMT3B) gene in ICF syndrome
 mutations in the MECP2 gene in the Rett syndrome, encoding a protein that binds to methylated DNA.

See also

 X-inactivation
 genomic imprinting
 genome stabilization
 5-methylcytosine

References

 Burgers WA, Fuks F, Kouzarides T. DNA methyltransferases get connected to chromatin. Trends Genet. 2002 Jun;18(6):275-7. PMID: #12044346#

 Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000 Oct;9(16):2395-402. PMID: #11005794#