Random Switching of the ModA11 Type III DNA Methyltransferase of Neisseria meningitidis Regulates Entner–Doudoroff Aldolase Expression by a Methylation Change in the eda Promoter Region

Jen, Freda E.-C.; Scott, Adeana L.; Tan, Aimee; Seib, Kate L.; Jennings, Michael P.

doi:10.1016/j.jmb.2020.08.024

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…A small number, however, will affect the expression of a subset of genes (the regulon or phasevarion, depending on the timescale). The example of modA11 in Neisseria meningitidis shows these effects can be either direct or indirect: Of 285 genes differentially regulated between the modA11 ON and OFF states (113), only 26 were directly regulated through methylation of the upstream intergenic region, while the remainder were likely indirectly regulated through perturbation of regulatory factor expression or key biological processes (61). Furthermore, it may be that epigenetic regulation of only a subset of the regulon or phasevarion confers any selective or phenotypic advantage, and determining which regulated genes are functionally important and which are coincidental is challenging.…”

Section: Conservation and Function Of Target Site-diverse Mtase Locimentioning

confidence: 99%

Beyond Restriction Modification: Epigenomic Roles of DNA Methylation in Prokaryotes

Anton

Roberts

2021

Annu. Rev. Microbiol.

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The amount of bacterial and archaeal genome sequence and methylome data has greatly increased over the last decade, enabling new insights into the functional roles of DNA methylation in these organisms. Methyltransferases (MTases), the enzymes responsible for DNA methylation, are exchanged between prokaryotes through horizontal gene transfer and can function either as part of restriction-modification systems or in apparent isolation as single (orphan) genes. The patterns of DNA methylation they confer on the host chromosome can have significant effects on gene expression, DNA replication, and other cellular processes. Some processes require very stable patterns of methylation, resulting in conservation of persistent MTases in a particular lineage. Other processes require patterns that are more dynamic yet more predictable than what is afforded by horizontal gene transfer and gene loss, resulting in phase-variable or recombination-driven MTase alleles. In this review, we discuss what is currently known about the functions of DNA methylation in prokaryotes in light of these evolutionary patterns. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Conservation and Function Of Target Site-diverse Mtase Locimentioning

confidence: 99%

Beyond Restriction Modification: Epigenomic Roles of DNA Methylation in Prokaryotes

Anton

Roberts

2021

Annu. Rev. Microbiol.

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“…All together, the three RMSs we examined account for 1818 distinct methylation sites that would vary in methylation status among the strains we studied. The number of intergenic methylation sites in UTI89, which are expected to be more likely to affect gene regulation (46,(77)(78)(79)(80), are comparable for the three Type I RMSs (31-40 intergenic sites) (S5 Table ). Using RNA-seq, we again found no gene expression changes for any of the "methylation-switch" strains compared with the parental wt UTI89, except for one hypothetical gene that was close to both the FDR and fold-change cutoffs (Fig 4C and 4D MG1655 and wt UTI89 at any concentration, consistent with our previous interpretation that the single difference identified between UTI89 and UTI89ΔhsdSMR was a false positive (Fig 1D, S4 Table ).…”

Section: Switching Type I Methylation Systems In Uti89 Also Does Not Affect Gene Expression or Any Growth Phenotypesmentioning

confidence: 99%

Methylation by multiple type I restriction modification systems avoids influencing gene regulation in uropathogenicEscherichia coli

Mehershahi

Chen

2021

Preprint

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DNA methylation is a common epigenetic mark that influences transcriptional regulation, and therefore cellular phenotype, across all domains of life, extending also to bacterial virulence. Both orphan methyltransferases and those from restriction modification systems (RMSs) have been co-opted to regulate virulence epigenetically in many bacteria. However, the potential regulatory role of DNA methylation mediated by archetypal Type I systems in Escherichia coli has never been studied. We demonstrated that removal of DNA methylated mediated by three different Escherichia coli Type I RMSs in three distinct E. coli strains had no detectable effect on gene expression or growth in a screen of 1190 conditions. Additionally, deletion of the Type I RMS EcoUTI in UTI89, a prototypical cystitis strain of E. coli, which led to loss of methylation at >750 sites across the genome, had no detectable effect on virulence in a murine model of ascending urinary tract infection (UTI). Finally, introduction of two heterologous Type I RMSs into UTI89 also resulted in no detectable change in gene expression or growth phenotypes. These results stand in sharp contrast with many reports of RMSs regulating gene expression in other bacteria, leading us to propose the concept of “regulation avoidance” for these E. coli Type I RMSs. We hypothesize that regulation avoidance is a consequence of evolutionary adaptation of both the RMSs and the E. coli genome. Our results provide a clear and (currently) rare example of regulation avoidance for Type I RMSs in multiple strains of E. coli, further study of which may provide deeper insights into the evolution of gene regulation and horizontal gene transfer.Author summaryDNA methylation is perhaps the most common epigenetic modification, and it is commonly associated with gene regulation (in nearly all organisms) and virulence (particularly well studied in bacteria). Regarding bacterial virulence, the current DNA methylation literature has focused primarily on orphan methyltransferases or phasevariable restriction modification systems (RMSs). Interestingly, no reports have studied the potential regulatory role of the first RMS discovered, the Type I RMS EcoKI. We used transcriptomics, Phenotype Microarrays, and a murine model of urinary tract infection to screen for functional consequences due to Type I methylation in three unrelated strains of E. coli. Remarkably, we found zero evidence for any epigenetic regulation mediated by these Type I RMSs. Thus, these Type I RMSs appear to function exclusively in host defense against incoming DNA (the canonical function of RMSs), while the methylation status of many hundreds of the corresponding recognition sites has no detectable impact on gene expression or any phenotypes. This led us to the concept of “regulation avoidance” by such DNA methyltransferases, which contrasts with the current literature on bacterial epigenetics. Our study hints at the existence of an entire class of regulation avoidant systems, which provides new perspectives on methylation-mediated gene regulation and bacterial genome evolution.

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DNA Methylation in Prokaryotes

Casadesús

Sánchez-Romero

2022

Advances in Experimental Medicine and Biology

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Random Switching of the ModA11 Type III DNA Methyltransferase of Neisseria meningitidis Regulates Entner–Doudoroff Aldolase Expression by a Methylation Change in the eda Promoter Region

Abstract: Random switching of the ModA11 type III DNA methyltransferase of Neisseria meningitidis regulates Entner-Doudoroff aldolase expression by a methylation change in the eda promoter region.

Cited by 7 publications

References 31 publications

Beyond Restriction Modification: Epigenomic Roles of DNA Methylation in Prokaryotes

Beyond Restriction Modification: Epigenomic Roles of DNA Methylation in Prokaryotes

Methylation by multiple type I restriction modification systems avoids influencing gene regulation in uropathogenicEscherichia coli

DNA Methylation in Prokaryotes

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