Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase

Barel, Itay; Naughton, Brigitte S.; Reich, Norbert O.; Brown, Frank L. H.

doi:10.1021/acs.jpcb.7b10349

Cited by 5 publications

(3 citation statements)

References 61 publications

(134 reference statements)

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“…Although the substrate sequences of Dam (GATC) and CcrM (GAnTC) are both palindromic, both enzymes act on hemi-methylated DNA substrates (Figure 2G - H ) – that is, sequences that already contain N6mA in one strand. Both enzymes can act on unmethylated sites, but most often encounter hemimethylated sites resulting from replication of fully-methylated sites, and both enzymes show a preference for hemimethylated over unmethylated sites ( 54 , 55 ).…”

Section: Introductionmentioning

confidence: 99%

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Woodcock

Horton

Zhang

et al. 2020

Nucleic Acids Research

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S-adenosyl-l-methionine dependent methyltransferases catalyze methyl transfers onto a wide variety of target molecules, including DNA and RNA. We discuss a family of methyltransferases, those that act on the amino groups of adenine or cytosine in DNA, have conserved motifs in a particular order in their amino acid sequence, and are referred to as class beta MTases. Members of this class include M.EcoGII and M.EcoP15I from Escherichia coli, Caulobacter crescentus cell cycle–regulated DNA methyltransferase (CcrM), the MTA1-MTA9 complex from the ciliate Oxytricha, and the mammalian MettL3-MettL14 complex. These methyltransferases all generate N6-methyladenine in DNA, with some members having activity on single-stranded DNA as well as RNA. The beta class of methyltransferases has a unique multimeric feature, forming either homo- or hetero-dimers, allowing the enzyme to use division of labor between two subunits in terms of substrate recognition and methylation. We suggest that M.EcoGII may represent an ancestral form of these enzymes, as its activity is independent of the nucleic acid type (RNA or DNA), its strandedness (single or double), and its sequence (aside from the target adenine).

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Section: Introductionmentioning

confidence: 99%

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Woodcock

Horton

Zhang

et al. 2020

Nucleic Acids Research

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“…Most previous studies on MTase kinetics focused on in vitro analysis [35] , [36] , [37] . Several analyses on in vivo methylation kinetics have been reported, including one publication on bacteria, but have not explored single-motif methylation kinetics [38] , [39] , [40] .…”

Section: Discussionmentioning

confidence: 99%

Precision Methylome and in Vivo Methylation Kinetics Characterization of Klebsiella Pneumoniae

Zhang

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

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Klebsiella pneumoniae (K. pneumoniae) is an important pathogen that can cause severe hospital- and community-acquired infections. To systematically investigate its methylation features, we determined the whole-genome sequences of 14 K. pneumoniae strains covering varying serotypes, multilocus sequence types, clonal groups, viscosity/virulence, and drug resistance. Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies. We identified 15 methylation motifs [13 N6-methyladenine (6 mA) and two 5-methylcytosine (5mC) motifs], among which eight were novel. Their corresponding DNA methyltransferases were also validated. Additionally, we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains, and identified differential distribution patterns of some hemi-/un-methylated GATC motifs, which tend to be located within intergenic regions (IGRs). Specifically, we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation. The slow methylation of the GATC motifs in the replication origin (oriC) regions and IGRs implicates the epigenetic regulation of replication initiation and transcription. Our findings illustrate the first comprehensive dynamic methylome map of K. pneumoniae at single-base resolution, and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

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“…Previous studies on MTase kinetics mainly focused on in vitro analysis [31−33]. Several reported analyses about the in vivo methylation kinetics, including one publication about bacteria, only studied the overall, but not single-motif methylation kinetics [34−36].…”

Section: Discussionmentioning

confidence: 99%

Precision Methylome andin vivoMethylation Kinetics Characterization ofKlebsiella Pneumoniae

Fu¹,

Zhang²,

Li³

et al. 2020

Preprint

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Klebsiella pneumoniae (K. pneumonia) is an important pathogen that can cause severe hospital-/community-acquired infections. To panoramically analyze K. pneumoniae’s methylation features, we completed the whole genome sequences of 14 K. pneumoniae strains covering various serotypes, multilocus-sequence typings (MLSTs), clonal groups (CG), viscosity/virulence and drug-resistances, and further characterized their methylomes using PacBio-SMRT and bisulfite technologies. We identified 15 methylation motifs (13 6mA and two 5mC motifs), among which eight were novel ones. Their corresponding MTases were further validated. Additionally, we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains, and identified differential distributive patterns of some hemi/un-methylated GATC motifs tending to locate in the intergenic regions (IGRs). Specifically, we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation. The slower methylation-rates of the GATC motifs in the replication origins (oriC) and IGRs suggest an epigenetic mechanism implicated in the regulation of replication-initiation and transcription. Our findings illustrate the first comprehensive dynamic methylome map of K. pneumonia at single base resolution, and provide an efficient means and important reference for a better understanding of epigenetic regulation in bacteria.

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Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase

Cited by 5 publications

References 61 publications

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Precision Methylome and in Vivo Methylation Kinetics Characterization of Klebsiella Pneumoniae

Precision Methylome andin vivoMethylation Kinetics Characterization ofKlebsiella Pneumoniae

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