Genetic Studies on Mammalian DNA Methyltransferases.
Cytosine methylation at the C5-position, generating 5-methylcytosine (5mC), is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80 %) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development. Aberrant changes in DNA methylation levels and patterns are associated with various human diseases, including cancer and developmental disorders. DNA methylation is mediated by three active DNA methyltransferases (Dnmts), namely, Dnmt1, Dnmt3a, and Dnmt3b, in mammals. Over the last two decades, genetic manipulations of these enzymes, as well as their regulators, in mice have greatly contributed to our understanding of the biological functions of DNA methylation in mammals. In this chapter, we discuss genetic studies on mammalian Dnmts, focusing on their roles in embryogenesis, cellular differentiation, genomic imprinting, and X-chromosome inactivation.
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX, 78957, USA.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX, 78957, USA.
Jiameng
J
Dan
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX, 78957, USA. tchen2@mdanderson.org.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX, 78957, USA. tchen2@mdanderson.org.|Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA. tchen2@mdanderson.org.
Taiping
T
Chen
D044503:5-Methylcytosine / Q000737:chemistry*; D000818:Animals; D002843:Chromatin / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D016678:Genome; D006801:Humans; D008322:Mammals; D051379:Mice
D002843:Chromatin; D044503:5-Methylcytosine; D004248:DNA (Cytosine-5-)-Methyltransferases
DNA methylation; Dnmt1; Dnmt3L; Dnmt3a; Dnmt3b; Genomic imprinting; X-chromosome inactivation