The role of epigenetic transcription repression and DNA methyltransferases in cancer

• Published in: Cancer Vol. 117; no. 4; pp. 677 - 687
• Main Authors: Daniel, Filipe Ivan, Cherubini, Karen, Yurgel, Liliane Soares, de Figueiredo, Maria Antonia Zancanaro, Salum, Fernanda Gonçalves
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2011; Wiley-Blackwell
• Subjects: Biological and medical sciences; Cancer; Carbon; CpG islands; Cytosine; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methylation; DNA methyltransferase; DNA-Cytosine Methylases - metabolism; Down-Regulation; Embryogenesis; Enzymes; epigenesis; Epigenesis, Genetic; epigenetics; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genomic instability; genomics; histone code; Histones; Humans; Medical sciences; methyltransferases; Neoplasms - genetics; Regulatory sequences; Transcription; Tumor suppressor genes; Tumors; Transcription; Enzyme; Transferases; Repression; Malignant tumor; Cancerology; Methyltransferases; epigenesis; Epigenetics; DNA methylation; histone code; Histone; Methylation; Cancer
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.25482

Epigenetic alterations such as DNA methylation have been implicated in the development and progression of various cancers. DNA methylation consists of the reversible addition of a methyl group to the carbon 5 position of cytosine in CpG dinucleotides and is considered essential for normal embryonic development. However, global genomic hypomethylation and aberrant hypermethylation of regulatory regions of tumor suppressor genes have been associated with chromosomal instability and transcription repression, respectively, providing neoplastic cells with a selective advantage. DNA methyltransferases are the enzymes responsible for the addition of methyl groups to CpG dinucleotides, which, together with histone modifiers, initiate the events necessary for transcription repression to occur. It has been demonstrated that increased expression of DNA methyltransferases may contribute to tumor progression through methylation‐mediated gene inactivation in various human cancers. Given their importance, this article reviews the main epigenetic mechanisms for regulating transcription and its implications in cancer development. Cancer 2011. © 2010 American Cancer Society.
Epigenetic alterations such as global genomic hypomethylation and aberrant hypermethylation of tumor suppressor genes have been implicated in the development of various cancers. As DNA methyltransferases may contribute to tumor progression through methylation‐mediated gene inactivation, this article reviewed the main epigenetic mechanisms for regulating transcription and its implication in cancer development.