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DNMT cooperativity—the developing links between methylation, chromatin structure and cancer
Author(s) -
ElOsta Assam
Publication year - 2003
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.10345
Subject(s) - dna methylation , epigenetics , biology , methylation , cancer epigenetics , cancer , methyltransferase , dnmt3b , dnmt1 , epigenetics of physical exercise , genetics , cancer research , gene , gene expression
Controversy has reigned for some time over the biological connection between DNA methylation and cancer. For this reason, the methylation mechanism responsible for increased cancer risk has received greater attention in recent years. Tumor suppressor genes are often hypermethylated resulting in gene silencing. Although some have questioned this interpretation of the link between methylation and cancer, it appears that both hypermethylation and hypomethylation events can create epigenetic changes that can contribute to cancer development. Recent studies have shown that the methyltransferases DNMT1 and DNMT3b cooperatively maintain DNA methylation and gene silencing in human cancer cells. Disruption of the human DNMT3b only slightly reduces the overall global DNA methylation; however, demethylation was markedly potentiated when both DNMT1 and DNMT3b were simultaneously deleted. The results to these experiments provide compelling evidence towards a role for DNA methylation in cancer. This review discusses the current understanding of cancer‐epigenetic information and highlights recent studies that connect the methylation machinery and chromatin remodelling with cancer susceptibility. BioEssays 25:1071–1084, 2003. © 2003 Wiley Periodicals, Inc.