Abstract
In this chapter we focus on the regulation and function of DNA methylation in mammals and especially in humans. We describe the main features of the enzymatic machinery generating 5-methylcytosine (5mC) that functions as an epigenetic mark in mammalian cells, and outline the active and passive mechanisms that can remove this reversible modification of DNA. We briefly introduce the characteristics of “maintenance” and “de novo” DNA-(cytosine-C5)-methyltransferases (DNMTs) and overview how their expression is regulated at the transcriptional, posttranscriptional, and posttranslational level. The interacting partners and chromatin marks involved in the targeting of DNMTs to the replication foci during S phase or to various chromatin domains during other phases of the cell cycle are also discussed. The enzymatic functions of DNMTs and their interactions with cellular macromolecules are involved in a series of cellular processes, some of them vital for mammals. Thus, DNA methylation has a role in the regulation of chromatin structure and promoter activity. It may silence the promoters of imprinted genes showing monoallelic expression as well as the promoters of transposons, and contributes to gene silencing on the inactive X chromosome, too. There are genome-wide demethylation and remethylation events during embryogenesis suggesting a regulatory role for DNA methylation in developmental processes, and both cytosine methylation and the active removal of 5mC from DNA is involved in the control of cell differentiation. DNA methylation plays a role in the preservation of genomic stability and gene body methylation affects the inclusion of certain exons into mature mRNA molecules by affecting – indirectly – the splicing of primary transcripts. Epigenetic regulatory mechanisms, including DNA methylation, are at the forefront of brain research these days. For this reason we outlined some of the most interesting results of this exciting new field in a separate subsection.
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Acknowledgments
This work was supported by the grant GINOP-2.3.2-15-2016-00011 to a consortium led by the University of Szeged, Szeged, Hungary (participants: the University of Debrecen, Debrecen, and the Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary), project leader Janos Minarovits. The grant was funded by the European Regional Development Fund of the European Union and managed in the framework of Economic Development and Innovation Operational Programme by the Ministry of National Economy, National Research, Development and Innovation Office, Budapest, Hungary.
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Niller, H.H., Demcsák, A., Minarovits, J. (2017). DNA Methylation in Eukaryotes: Regulation and Function. In: Krell, T. (eds) Cellular Ecophysiology of Microbe. Handbook of Hydrocarbon and Lipid Microbiology . Springer, Cham. https://doi.org/10.1007/978-3-319-20796-4_24-1
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