[S8-4] Networking and specificity-changing DNA methyltransferases in H. pylori
Epigenetic DNA base methylation plays important roles in gene expression regulation. We here describe a regulation network consisting of many DNA methyltransferases each frequently changing its target sequence-specificity. Our object H. pylori carries a large and variable repertoire of sequence-specific methyltransferases. By knocking out a dozen of them, we revealed they form a network controlling methylome, transcriptome and adaptive phenotype sets. The methyltransferases interact with each other in a hierarchical way, sometimes regulated positively by one methyltransferase but negatively with another. Motility, oxidative stress tolerance and DNA damage repair are likewise regulated by multiple methyltransferases. Their regulation sometimes involves translation start and stop codons suggesting coupling of methylation, transcription and translation. The methyltransferases change their sequence-specificity through gene conversion of their target recognition domain and switch their target sets to remodel the network. The emerging picture of a metamorphosing gene regulation network, or firework, consisting of mobile and changing epigenetic systems, in search for adaptation provides a new paradigm in pathogenesis and evolution.
600 global methylomes from HpGenomeProject will provide further insights into their action and roles.
600 global methylomes from HpGenomeProject will provide further insights into their action and roles.