scholarly journals DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

2018 ◽  
Author(s):  
Timothy Casselli ◽  
Yvonne Tourand ◽  
Adam Scheidegger ◽  
William K. Arnold ◽  
Anna Proulx ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Expression Profiles ◽  
Geographical Area ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

ABSTRACTProkaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The causative agent of Lyme disease,Borrelia burgdorferi, encodes two RM systems with N6-Methyladenosine (m6A) MTase activity. The specific recognition and/or methylation sequences have not been identified for eitherB. burgdorferiMTase, and it is not currently known whether these RM systems influence transcriptome profiles. In the current study, Single Molecule Real Time sequencing was utilized to map genome-wide m6A sites, and to identify consensus modified motifs in wild-typeB. burgdorferias well as isogenic MTase mutants. Four conserved m6A motifs were identified, and were fully attributable to the presence of specific MTases. Whole-genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, indicating that DNA methylation by RM systems has effects on gene expression inB. burgdorferi. The results of this study provide a comprehensive view of the DNA methylation pattern inB. burgdorferi, and the accompanying gene expression profiles add to the emerging body of research on RM systems and gene regulation in bacteria.IMPORTANCELyme disease is the most prevalent vector-borne disease in North America, and is classified by the Centers for Disease Control and Prevention (CDC) as an emerging infectious disease with an expanding geographical area of occurrence. Previous studies have shown that the causative bacterium,Borrelia burgdorferi, methylates its genome using restriction modification systems that allow for the distinction of self from foreign DNA. Although much research has focused on the regulation of gene expression inB. burgdorferi, the effects of DNA methylation on gene regulation has not been evaluated. The current study characterizes the patterns of DNA methylation by restriction modification systems inB. burgdorferi, and evaluates the resulting effects on gene regulation in this important pathogen.

scholarly journals DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

2018 ◽  
Vol 200 (24) ◽  
Author(s):  
Timothy Casselli ◽  
Yvonne Tourand ◽  
Adam Scheidegger ◽  
William K. Arnold ◽  
Anna Proulx ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Expression Profiles ◽  
Content Type ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

ABSTRACTProkaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease,Borrelia burgdorferiB31, possesses two RM systems withN6-methyladenosine (m6A) MTase activity, which are encoded by thebbe02gene located on linear plasmid lp25 andbbq67on lp56. The specific recognition and/or methylation sequences had not been identified for either of theseB. burgdorferiMTases, and it was not previously known whether these RM systems influence transcript levels. In the current study, single-molecule real-time sequencing was utilized to map genome-wide m6A sites and to identify consensus modified motifs in wild-typeB. burgdorferias well as MTase mutants lacking either thebbe02gene alone or bothbbe02andbbq67genes. Four novel conserved m6A motifs were identified and were fully attributable to the presence of specific MTases. Whole-genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, indicating that DNA methylation by the RM systems has effects on gene expression. Genes with altered transcription in MTase mutants include those involved in vertebrate host colonization (e.g.,rpoSregulon) and acquisition by/transmission from the tick vector (e.g.,rrp1andpdeB). The results of this study provide a comprehensive view of the DNA methylation pattern inB. burgdorferi, and the accompanying gene expression profiles add to the emerging body of research on RM systems and gene regulation in bacteria.IMPORTANCELyme disease is the most prevalent vector-borne disease in North America and is classified by the Centers for Disease Control and Prevention (CDC) as an emerging infectious disease with an expanding geographical area of occurrence. Previous studies have shown that the causative bacterium,Borrelia burgdorferi, methylates its genome using restriction modification systems that enable the distinction from foreign DNA. Although much research has focused on the regulation of gene expression inB. burgdorferi, the effect of DNA methylation on gene regulation has not been evaluated. The current study characterizes the patterns of DNA methylation by restriction modification systems inB. burgdorferiand evaluates the resulting effects on gene regulation in this important pathogen.

scholarly journals Methylation by multiple type I restriction modification systems avoids influencing gene regulation in uropathogenic Escherichia coli

2021 ◽  
Author(s):  
Kurosh S Mehershahi ◽  
Swaine Chen
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Detectable Effect ◽  
Epigenetic Mark ◽  
Type I ◽  
E Coli ◽  
Restriction Modification ◽  
Restriction Modification Systems

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.

scholarly journals Epigenomic Landscape of Lyme Disease Spirochetes Reveals Novel Motifs

mBio ◽  
2021 ◽  
Author(s):  
Jenny Wachter ◽  
Craig Martens ◽  
Kent Barbian ◽  
Ryan O. M. Rego ◽  
Patricia Rosa
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Type Strain ◽  
Species Complex ◽  
The United States ◽  
Content Type ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

The principal causative agent of Lyme disease in humans in the United States is Borrelia burgdorferi , while B. burgdorferi , B. afzelii , and B. garinii , collectively members of the Borrelia burgdorferi sensu lato species complex, cause Lyme disease in Europe and Asia. Two plasmid-encoded restriction/modification systems have been shown to limit the genetic transformation of B. burgdorferi type strain B31 with foreign DNA, but little is known about the restriction/modification systems of other Lyme disease Borrelia bacteria.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals DNA Methylation and RNA-Sequencing Analysis Show Epigenetic Function During Grain Filling in Foxtail Millet (Setaria italica L.)

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Wang ◽  
Quanwei Lu ◽  
Hui Song ◽  
Nan Hu ◽  
Yangyang Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Potential Function ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Dynamic Change ◽  
Foxtail Millet ◽  
Grain Filling ◽  
Sequencing Analysis ◽  
Grain Development

Grain filling is a crucial process for crop yield and quality. Certain studies already gained insight into the molecular mechanism of grain filling. However, it is unclear whether epigenetic modifications are associated with grain filling in foxtail millet. Global DNA methylation and transcriptome analysis were conducted in foxtail millet spikelets during different stages to interpret the epigenetic effects of the grain filling process. The study employed the whole-genome bisulfite deep sequencing and advanced bioinformatics to sequence and identify all DNA methylation during foxtail millet grain filling; the DNA methylation-mediated gene expression profiles and their involved gene network and biological pathway were systematically studied. One context of DNA methylation, namely, CHH methylation, was accounted for the largest percentage, and it was gradually increased during grain filling. Among all developmental stages, the methylation levels were lowest at T2, followed by T4, which mainly occurred in CHG. The distribution of differentially methylated regions (DMR) was varied in the different genetic regions for three contexts. In addition, gene expression was negatively associated with DNA methylation. Evaluation of the interconnection of the DNA methylome and transcriptome identified some stage-specific differentially expressed genes associated with the DMR at different stages compared with the T1 developmental stage, indicating the potential function of epigenetics on the expression regulation of genes related to the specific pathway at different stages of grain development. The results demonstrated that the dynamic change of DNA methylation plays a crucial function in gene regulation, revealing the potential function of epigenetics in grain development in foxtail millet.

scholarly journals Identification of Prognostic Markers in Cholangiocarcinoma Using Altered DNA Methylation and Gene Expression Profiles

2020 ◽  
Vol 11 ◽  
Author(s):  
Nitish Kumar Mishra ◽  
Meng Niu ◽  
Siddesh Southekal ◽  
Prachi Bajpai ◽  
Amr Elkholy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals DNA methylation from a Type I restriction modification system influences gene expression and virulence in Streptococcus pyogenes

2019 ◽  
Vol 15 (6) ◽  
pp. e1007841 ◽  
Author(s):  
Taylor M. Nye ◽  
Kristin M. Jacob ◽  
Elena K. Holley ◽  
Juan M. Nevarez ◽  
Suzanne Dawid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Streptococcus Pyogenes ◽  
Type I ◽  
Modification System ◽  
Restriction Modification System ◽  
Restriction Modification

152 SPECIES-SPECIFIC DIFFERENCES IN THE METHYLATION REPROGRAMMING DURING EARLY PRE-IMPLANTATION DEVELOPMENT

2017 ◽  
Vol 29 (1) ◽  
pp. 184
Author(s):  
S. Canovas ◽  
E. Ivanova ◽  
S. Garcia-Martinez ◽  
R. Romar ◽  
N. Fonseca-Balvis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Gene Expression Pattern ◽  
Reproductive Technologies ◽  
Global Methylation ◽  
Species Specific

Studies in mouse and human have shown extensive DNA methylation reprogramming in pre-implantation development followed by remethylation from implantation. However, the extent to which such reprogramming is conserved in mammals and the timing of demethylation and remethylation are unknown. As part of a major objective to characterise methylation dynamics in the bovine and porcine species from the oocyte to the blastocyst stage, we aimed here to compare the distribution of methylation at single-base resolution in both species at Day 7.5 of development. The DNA methylation profiles were obtained from individual blastocysts at Day 7.5 [pig: 3 in vivo, 3 in vitro; cow: 3 in vivo, 3 in vitro, 3 inner cell mass (ICM) and 3 trophoectoderm (TE) dissected from in vitro blastocysts] using the post-bisulphite adaptor tagging method and Illumina sequencing. For oocytes, data (GEO: GSE63330) from Schroeder et al. 2015 were analysed. Raw sequences were mapped, methylation calls made using Bismark and data analysis and visualisation was done within the SeqMonk platform. Gene expression profiles from individual blastocysts (3 pig, 3 cow) were obtained by RNA-seq. Annotated mRNA features were quantitated in SeqMonk and these were fed into DESeq2 for differential expression analysis (P < 0.05) as previously reported (Love et al. 2014 Genome Biol. 15, 550). Global methylation levels in whole blastocysts differed substantially between porcine and bovine embryos (in vivo: 12.33 ± 3.6 v. 28.33 ± 3.5%; in vitro: 15.02 ± 3.3 v. 24.41 ± 4.1%). In addition, the distribution of methylation differed: the pattern of cytosine methylated seemed random in the porcine genome, but was highly structured in the bovine genome, with methylation predominantly over gene bodies, resembling the profile previously reported in oocytes (Schroeder et al. 2015 PLoS Genet. 11, e1005442). Regarding correlation analysis, gene expression versus methylation were plotted. It suggested that gene body methylation reflected gene expression pattern in oocytes as well as in bovine blastocysts. Pair-wise comparison of isolated ICM and TE was filtered to require 5% change, and replicate set statistics were applied. This revealed very similar total and regional methylation levels in the 2 compartments, indicating that remethylation does not initiate preferentially in one compartment in bovine pre-implantation embryos. This confirms, from a viewpoint of the genome-wide DNA methylation, what has been observed in mouse for specific genes: the trophoblast-specific DNA methylation occurs after the segregation of the TE and ICM (Nakanishi et al. 2012 Epigenetics 7, 173–183). Our study is the first to provide whole genome methylation profiles from single blastocysts of economically important livestock species. Our data demonstrate that methylation reprogramming in early pre-implantation development is species specific. Knowledge of these specific patterns may have high importance when decisions are taken regarding the use of assisted reproductive technologies, cloning, or generation of transgenic animals. This work was funded by AGL2015–66341-R (MINECO-FEDER), PRX14/00348 (MECD), 19595/EE/14 (F. Séneca).

scholarly journals DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ieva Rauluseviciute ◽  
Finn Drabløs ◽  
Morten Beck Rye
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Normal Tissue ◽  
Expression Profiles ◽  
Expression Data ◽  
Dna Hypermethylation ◽  
Genome Wide ◽  
A Genome

Abstract Background Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts. DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation. Such additional complexity could have important implications for understanding prostate cancer development but has not been studied at a genome-wide scale. Results In this study, we have compared three sets of genome-wide single-site DNA methylation data from 870 PCa and normal tissue samples with multi-cohort gene expression data from 1117 samples, including 532 samples where DNA methylation and gene expression have been measured on the exact same samples. Genes were classified according to their corresponding methylation and expression profiles. A large group of hypermethylated genes was robustly associated with increased gene expression (UPUP group) in all three methylation datasets. These genes demonstrated distinct patterns of correlation between DNA methylation and gene expression compared to the genes showing the canonical negative association between methylation and expression (UPDOWN group). This indicates a more diversified role of DNA methylation in regulating gene expression than previously appreciated. Moreover, UPUP and UPDOWN genes were associated with different compartments — UPUP genes were related to the structures in nucleus, while UPDOWN genes were linked to extracellular features. Conclusion We identified a robust association between hypermethylation and upregulation of gene expression when comparing samples from prostate cancer and normal tissue. These results challenge the classical view where DNA methylation is always associated with suppression of gene expression, which underlines the importance of considering corresponding expression data when assessing the downstream regulatory effect of DNA methylation.

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