Mechanisms and biological roles of DNA methyltransferases and DNA methylation: From past achievements to future challenges

DNA methylation and DNA methyltransferases (MTases)—the enzymes that introduce the methylation mark into the DNA—have been studied for almost 70 years. In this chapter, we review the key developments in the DNA methylation field that have led to our current understanding of the structures and mechanisms of DNA MTases. We discuss the essential biological roles of DNA methylation, including the discovery of DNA methylation, cloning and sequence analysis of the bacterial and eukaryotic MTases, and the elucidation of their structure, mechanism, regulation, and molecular evolution. We describe genetic studies that contributed greatly to the evolving views on the role of DNA methylation in development and diseases, the invention of methods for the genome-wide analysis of DNA methylation, and the biochemical identification of DNA MTases and the TET enzyme family, which is involved in DNA demethylation. We summarize the roles of MTases in bacterial epigenetics and the application of MTases in synthetic biology to generate artificial signaling systems. We finish by highlighting some open questions for the next years of research in the field