Networking and Specificity-Changing DNA Methyltransferases in Helicobacter pylori.

Hirokazu Yano,Yoshikazu Furuta,Tomoko F Shibata,Keigo Shibayama,Yutaka Suzuki,Mitsuyasu Hasebe,Shuji Shigenobu,Sumio Sugano,Atsushi Toyoda,Ichizo Kobayashi,Emiko Rimbara,Tomoaki Nishiyama,Md Zobaidul Alam,Masaki Fukuyo

doi:10.3389/fmicb.2020.01628

Abstract

Epigenetic DNA base methylation plays important roles in gene expression regulation. We here describe a gene expression regulation network consisting of many DNA methyltransferases each frequently changing its target sequence-specificity. Our object Helicobacter pylori, a bacterium responsible for most incidence of stomach cancer, carries a large and variable repertoire of sequence-specific DNA methyltransferases. By creating a dozen of single-gene knockout strains for the methyltransferases, we revealed that 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 frequently 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 epigenetic systems ever-changing their specificity in search for adaptation, provides a new paradigm in understanding global gene regulation and adaptive evolution.

Highlights

The currently dominating model for adaptive evolution assuming selection from diverse genome sequences is derived from genetics and molecular biology of microorganisms and other forms of life, but its general validity became thoroughly testable only recently with the availability of many genome sequences within a species
We knocked out each of the specificity-determinant genes of a total of 10 known/putative DNA methylation systems (Figure 2A) in two laboratory strains, P12 and 26695. Both belong to hpEurope population (Backert and Yamaoka, 2016), they differ in the repertoire of RM systems (Figure 1B)
Type I RM systems are composed of three subunits: a restriction (R) enzyme subunit, a methyltransferase (M) subunit, and a specificity (S) subunit usually with two target recognition domains (TRDs)

Summary

Introduction

The currently dominating model for adaptive evolution assuming selection from diverse genome sequences is derived from genetics and molecular biology of microorganisms and other forms of life, but its general validity became thoroughly testable only recently with the availability of many genome sequences within a species. A DNA methyltransferase (MTase) is often paired with a restriction enzyme to form a restrictionmodification (RM) system (Roberts et al, 2003). They form a prokaryotic immune system attacking non-self DNA lacking proper epigenetic DNA methylation and behave as selfish mobile elements (Vasu and Nagaraja, 2013)

Methods

Results

Conclusion