Dataset Information

CpG underrepresentation and the bacterial CpG-specific DNA methyltransferase M.MpeI.

ABSTRACT: Cytosine methylation promotes deamination. In eukaryotes, CpG methylation is thought to account for CpG underrepresentation. Whether scarcity of CpGs in prokaryotic genomes is diagnostic for methylation is not clear. Here, we report that Mycoplasms tend to be CpG depleted and to harbor a family of constitutively expressed or phase variable CpG-specific DNA methyltransferases. The very CpG poor Mycoplasma penetrans and its constitutively active CpG-specific methyltransferase M.MpeI were chosen for further characterization. Genome-wide sequencing of bisulfite-converted DNA indicated that M.MpeI methylated CpG target sites both in vivo and in vitro in a locus-nonselective manner. A crystal structure of M.MpeI with DNA at 2.15-Å resolution showed that the substrate base was flipped and that its place in the DNA stack was taken by a glutamine residue. A phenylalanine residue was intercalated into the "weak" CpG step of the nonsubstrate strand, indicating mechanistic similarities in the recognition of the short CpG target sequence by prokaryotic and eukaryotic DNA methyltransferases.

SUBMITTER: Wojciechowski M

PROVIDER: S-EPMC3538198 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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CpG underrepresentation and the bacterial CpG-specific DNA methyltransferase M.MpeI.

Wojciechowski Marek M Czapinska Honorata H Bochtler Matthias M

Proceedings of the National Academy of Sciences of the United States of America 20121217 1

Cytosine methylation promotes deamination. In eukaryotes, CpG methylation is thought to account for CpG underrepresentation. Whether scarcity of CpGs in prokaryotic genomes is diagnostic for methylation is not clear. Here, we report that Mycoplasms tend to be CpG depleted and to harbor a family of constitutively expressed or phase variable CpG-specific DNA methyltransferases. The very CpG poor Mycoplasma penetrans and its constitutively active CpG-specific methyltransferase M.MpeI were chosen fo ...[more]

PMID: 23248272

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Project description:Bacterial infections in the genital tract frequently result in morbidity through a variety of inflammation based symptoms. One component of the bacteria that may trigger host inflammatory response is their DNA. CpG motifs in this DNA are known targets for Toll-like receptor 9 (TLR9), which is a pathogen-recognition receptors focusing on CpG DNA. The activation of TLR9 induces the NF-?B inflammatory pathway. This study aims to provide a broad view of the inflammatory potential of CpG DNA motifs in bacteria related to genital diseases: C. trachomatis, E. coli, N. gonorrhoeae, G. vaginalis, H. ducreyi, L. crispatus, L. gasseri, M. hominis, M. genitalium, T. pallidum, and U. urealyticum.Publicly available genomic sequences of the bacterial species and strains have been analyzed in silico to produce a CpG index number. This CpG index number shows the relative inflammatory potential of the genome and has previously been used in a study by Lundberg et al. (2003). Higher CpG index values suggest a strong CpG induced inflammation potential during infection and vice versa.The highest observed CpG index belongs to G. vaginalis with a value of 26,2, suggesting a strong pro-inflammatory potential when in contact with TLR9. The lowest index belongs to N. gonorrhoeae with a value of -79,5, suggesting a strong immunoinhibitory effect on TLR9 contact. Interestingly, Lactobacilli showed a mean CpG index value of 4,2, suggesting a weak inflammatory potential.Our results show varying CpG index values between bacterial species. Comparison of CpG indices with the clinical course of several pathogens shows the CpG index helps clarify the clinical course of infection. However, we found no links between CpG index values and either obligate pathogenicity or facultative pathogenicity through bacterial vaginosis. Lactobacilli showed relatively low CpG indices which do suggest a lower inflammatory potential from these bacteria.Our results show varying CpG index values between bacterial species, which may help clarify the clinical course of infection, and may help diagnosis.

Dataset Information

CpG underrepresentation and the bacterial CpG-specific DNA methyltransferase M.MpeI.

Publications

CpG underrepresentation and the bacterial CpG-specific DNA methyltransferase M.MpeI.

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