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Methylation of DNA at cytosine residues plays an important role in regulation of gene expression, genomic imprinting and is essential for mammalian development. Hypermethylation of CpG islands in tumor suppressor genes or hypomethylation of bulk genomic DNA may be linked with development of cancer. To date, 3 families of mammalian DNA methyltransferase genes have been identified which include Dnmt1, Dnmt2 and Dnmt3.
Dnmt1 is constitutively expressed in proliferating cells and inactivation of this gene causes global demethylation of genomic DNA and embryonic lethality.
Dnmt2 is expressed at low levels in adult tissues and its inactivation does not affect DNA methylation or maintenance of methylation.
The Dnmt3 family members, Dnmt3a and Dnmt3b, are strongly expressed in ES cells but their expression is down regulated in differentiating ES cells and is low in adult somatic tissue. Recently, it has been shown that naturally occurring mutations of Dnmt3b gene occurs in patients! with a rare autosomal recessive disorder, termed ICF (immunodeficiency, centromeric instability, and facial anomalies) syndrome. http://www.imgenex.com