Shaping eukaryotic epigenetic systems by horizontal gene transfer

DNA methylation constitutes one of the pillars of epigenetics, relying on covalent bonds for addition and/or removal of chemically distinct marks within the major groove of the double helix. DNA methyltransferases, enzymes which introduce methyl marks, initially evolved in prokaryotes as components of restriction-modification systems protecting host genomes from bacteriophages and other invading foreign DNA. In early eukaryotic evolution, DNA methyltransferases were horizontally transferred from bacteria into eukaryotes several times and independently co-opted into epigenetic regulatory systems, primarily via establishing connections with the chromatin environment. While C5-methylcytosine is the cornerstone of plant and animal epigenetics and has been investigated in much detail, the epigenetic role of other methylated bases is less clear. The recent addition of N4-methylcytosine of bacterial origin as a metazoan DNA modification highlights the prerequisites for foreign gene co-option into the host regulatory networks, and challenges the existing paradigms concerning the origin and evolution of eukaryotic regulatory systems.

Automated summary

DNA methylation is a prominent feature of epigenetics, with DNA methyltransferases being transferred from prokaryotes to eukaryotes and co-opted into epigenetic regulatory systems. While the role of C5-methylcytosine in epigenetics is well-studied, the epigenetic effects of other methylated bases are less understood. The discovery of N4-methylcytosine of bacterial origin in metazoan DNA challenges the existing paradigms of eukaryotic regulatory systems' origin and evolution.