Abstract
Epigenetic modifications such as DNA methylation have large effects on gene expression and genome maintenance. Helicobacter pylori, a human gastric pathogen, has a large number of DNA methyltransferase genes, with different strains having unique repertoires. Previous genome comparisons suggested that these methyltransferases often change DNA sequence specificity through domain movement—the movement between and within genes of coding sequences of target recognition domains. Using single-molecule real-time sequencing technology, which detects N6-methyladenines and N4-methylcytosines with single-base resolution, we studied methylated DNA sites throughout the H. pylori genome for several closely related strains. Overall, the methylome was highly variable among closely related strains. Hypermethylated regions were found, for example, in rpoB gene for RNA polymerase. We identified DNA sequence motifs for methylation and then assigned each of them to a specific homology group of the target recognition domains in the specificity-determining genes for Type I and other restriction-modification systems. These results supported proposed mechanisms for sequence-specificity changes in DNA methyltransferases. Knocking out one of the Type I specificity genes led to transcriptome changes, which suggested its role in gene expression. These results are consistent with the concept of evolution driven by DNA methylation, in which changes in the methylome lead to changes in the transcriptome and potentially to changes in phenotype, providing targets for natural or artificial selection.
Highlights
Epigenetic modifications affect gene regulation and genome maintenance [1,2]
Most DNA methylation is by DNA methyltransferases with high sequence specificity
Helicobacter pylori, a human stomach pathogen responsible for stomach cancer and other diseases, carries a large number of DNA methyltransferase genes that vary among strains
Summary
Epigenetic modifications affect gene regulation and genome maintenance [1,2]. DNA methylation is an important epigenetic modification in bacteria with functions in gene expression regulation, genome replication initiation, cell cycle regulation, anti-mutagenesis, and genome maintenance [3,4]. Eukaryotes use a few DNA methyltransferases to mainly methylate DNA at CpG and other low-specificity sequences. DNA is methylated by a variety of DNA methyltransferases, most of which have high sequence specificity. Methylations in both promoter and coding regions affect gene expression [2,5,6]. Methyltransferases are often members of restriction-modification (RM) systems [7] and are called modification (M) enzymes
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