Genetic alterations of DNA methylation machinery in human diseases.
DNA methylation plays a critical role in the regulation of chromatin structure and gene expression and is involved in a variety of biological processes. The levels and patterns of DNA methylation are regulated by both DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and 'demethylating' proteins, including the ten-eleven translocation (TET) family of dioxygenases (TET1, TET2 and TET3). The effects of DNA methylation on chromatin and gene expression are largely mediated by methylated DNA 'reader' proteins, including MeCP2. Numerous mutations in DNMTs, TETs and MeCP2 have been identified in cancer and developmental disorders, highlighting the importance of the DNA methylation machinery in human development and physiology. In this review, we describe these mutations and discuss how they may lead to disease phenotypes.
Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park - Research Division, 1808 Park Road 1C, P. O. Box 389, Smithville, TX 78957, USA.
Tewfik
T
Hamidi
Anup Kumar
AK
Singh
Taiping
T
Chen
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004194:Disease / Q000235:genetics*; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D006899:Mixed Function Oxygenases; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics
D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D011518:Proto-Oncogene Proteins; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
AML; DNA methylation; DNMT; ICF syndrome; MBD; MeCP2; Rett syndrome; TET