scholarly journals Beyond a ribosomal RNA methyltransferase, the wider role of MraW in DNA methylation, motility and colonization inEscherichia coliO157:H7

2018 ◽  
Author(s):  
Xuefang Xu ◽  
Heng Zhang ◽  
Ying Huang ◽  
Yuan Zhang ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
16S Rrna ◽  
Dna Sequences ◽  
Fine Tuning ◽  
Flagellar Gene ◽  
Gene Sequences ◽  
Altered Expression ◽  
Genome Wide ◽  
Dna Methylase ◽  
Flagellar Genes

ABSTRACTMraW (RsmH) is an AdoMet-dependent 16S rRNA methyltransferase conserved in bacteria and plays a role in the fine-tuning of the ribosomal decoding center. It was recently found to contribute to the virulence ofStaphylococcus aureusin host animals. In this study, we examined the function of MraW inEscherichia coliO157:H7 and found that deletion ofmraWled to decreased motility and flagellar production. Whole-genome bisulfite sequencing showed genome wide decrease of methylation of 336 genes and 219 promoters in themraWmutant. The methylation level of 4 flagellar gene sequences were further confirmed by bisulfite PCR sequencing. Quantitative reverse transcription PCR results indicated the transcription of these genes was also affected. MraW was observed to directly bind to the four flagellar gene sequences by electrophoretic mobility shift assay (EMSA). A common motif in differentially methylated regions of promoters and coding regions of the 4 flagellar genes was identified. Reduced methylation was correlated with altered expression of 21 of the 24 genes tested. DNA methylation activity of MraW was confirmed by DNA methyltransferase (DNMT) activity assayin vitro. ThemraWmutant colonized poorer than wild type in mice. we further found that the expression ofmraZin themraWmutant was increased confirming the antagonistic effect ofmraWonmraZ. In conclusion,mraWwas found to be a DNA methylase and has a wide-ranging effect onE.coliO157:H7 including motility and virulencein vivovia genome wide methylation andmraZantagonism.IMPORTANCEMraW is a well-studied 16S rRNA methyltransferase and was recently found have an impact on bacterial virulence. Here we demonstrated its new function as a DNA methylase and effect on motility, colonization in mice, DNA methylation in genome wide and contribution to virulence. Its direct binding of differentially methylated flagellar-encoding DNA sequences was observed, indicating a correlation between DNA methylation and regulation of flagellar genes. In addition, the expression ofmraZwhich function as an antagonist ofmraWwas increased in themraWmutant.mraWplays an important role in gene regulation likely through DNA methylation. Clearly it plays a role in virulence inE. coliO157:H7. It also opens a new research field for virulence study in bacteria.

scholarly journals DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome

2021 ◽  
Author(s):  
Yanrong Ji ◽  
Zhihan Zhou ◽  
Han Liu ◽  
Ramana V Davuluri
Keyword(s):  
Dna Sequences ◽  
Regulatory Elements ◽  
Ease Of Use ◽  
Fine Tuning ◽  
Supplementary Information ◽  
Sequence Motifs ◽  
Semantic Relationship ◽  
Accurate Identification ◽  
Conserved Sequence ◽  
Genome Wide

Abstract Motivation Deciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. Results To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, to capture global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We compared DNABERT to the most widely used programs for genome-wide regulatory elements prediction and demonstrate its ease of use, accuracy and efficiency. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on prediction of promoters, splice sites and transcription factor binding sites, after easy fine-tuning using small task-specific labeled data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variant candidates. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance. We anticipate that the pre-trained DNABERT model can be fined tuned to many other sequence analyses tasks. Availability and implementation The source code, pretrained and finetuned model for DNABERT are available at GitHub (https://github.com/jerryji1993/DNABERT). Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6348
Author(s):  
Samrat Roy Choudhury ◽  
Cody Ashby ◽  
Fenghuang Zhan ◽  
Frits van Rhee
Keyword(s):  
Dna Methylation ◽  
Multiple Myeloma ◽  
Dna Sequences ◽  
Critical Length ◽  
Newly Diagnosed ◽  
Genome Wide ◽  
Healthy Donors ◽  
Binding Factor ◽  
G Quadruplex

High-risk Multiple Myeloma (MM) patients were found to maintain telomere length (TL), below the margin of short critical length, consistent with proactive overexpression of telomerase. Previously, DNA methylation has been shown as a determinant of telomere-related gene (TRG) expression and TL to assess risk in different types of cancer. We mapped genome-wide DNA methylation in a cohort of newly diagnosed MM (NDMM; n = 53) patients of major molecular subgroups, compared to age-matched healthy donors (n = 4). Differential methylation and expression at TRG-loci were analyzed in combination with overlapping chromatin marks and underlying DNA-sequences. We observed a strong correlation (R2 ≥ 0.5) between DNA methylation and expression amongst selective TRGs, such that demethylation at the promoters of DDX1 and TERF1 were associated to their oncogenic upregulation, while demethylation at the bodies of two key tumor suppressors ZNF208 and RAP1A led to downregulation of the genes. We demonstrated that TRG expression may be controlled by DNA methylation alone or in cooperation with chromatin modifications or CCCTC-binding factor at the regulatory regions. Additionally, we showed that hypomethylated DMRs of TRGs in NDMM are stabilized with G-quadruplex forming sequences, suggesting a crucial role of these epigenetically vulnerable loci in MM pathogenesis. We have identified a panel of five TRGs, which are epigenetically deregulated in NDMM patients and may serve as early detection biomarkers or therapeutic targets in the disease.

scholarly journals In utero Bisphenol A Exposure Is Linked with Sex Specific Changes in the Transcriptome and Methylome of Human Amniocytes

2019 ◽  
Vol 105 (2) ◽  
pp. 453-467
Author(s):  
Amita Bansal ◽  
Nicole Robles-Matos ◽  
Paul Zhiping Wang ◽  
David E Condon ◽  
Apoorva Joshi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisphenol A ◽  
Gestational Age ◽  
Molecular Mechanisms ◽  
In Utero ◽  
Metabolic Dysfunction ◽  
Altered Expression ◽  
Obesity And Diabetes ◽  
Genome Wide

Abstract Context Prenatal exposure to bisphenol A (BPA) is linked to obesity and diabetes but the molecular mechanisms driving these phenomena are not known. Alterations in deoxyribonucleic acid (DNA) methylation in amniocytes exposed to BPA in utero represent a potential mechanism leading to metabolic dysfunction later in life. Objective To profile changes in genome-wide DNA methylation and expression in second trimester human amniocytes exposed to BPA in utero. Design A nested case-control study was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Cases had amniotic fluid BPA measuring 0.251 to 23.74 ng/mL. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing (RNA-seq) were performed to determine differentially methylated regions (DMRs) and gene expression changes associated with BPA exposure. Ingenuity pathway analysis was performed to identify biologically relevant pathways enriched after BPA exposure. In silico Hi-C analysis identified potential chromatin interactions with DMRs. Results There were 101 genes with altered expression in male amniocytes exposed to BPA (q < 0.05) in utero, with enrichment of pathways critical to hepatic dysfunction, collagen signaling and adipogenesis. Thirty-six DMRs were identified in male BPA-exposed amniocytes and 14 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 24 genes with expression changes in male amniocytes and 12 in female amniocytes (P < 0.05). Conclusion In a unique repository of human amniocytes exposed to BPA in utero, sex-specific analyses identified gene expression changes in pathways associated with metabolic disease and novel DMRs with potential distal regulatory functions.

scholarly journals Description of three Rhacophorus tadpoles (Lissamphibia: Anura: Rhacophoridae) from Sarawak, Malaysia (Borneo)

Zootaxa ◽  
2012 ◽  
Vol 3328 (1) ◽  
pp. 1 ◽  
Author(s):  
ALEXANDER HAAS ◽  
STEFAN T. HERTWIG ◽  
WENKE KRINGS ◽  
ENZO BRASKAMP ◽  
J. MAXIMILIAN DEHLING ◽  
...  
Keyword(s):  
16S Rrna ◽  
Dna Barcoding ◽  
Dna Sequences ◽  
National Park ◽  
External Morphology ◽  
Gene Sequences ◽  
Respective Species

This communication reports the discovery of the hitherto unknown larval forms of Rhacophorus rufipes and R. penanorum, andre-describes the tadpole of R. dulitensis. Tadpoles of all three species were discovered at Gunung Mulu National Park, Sarawak(Borneo), Malaysia. The identity of the larvae was determined by DNA barcoding techniques using partial 16S rRNA mito-chondrial gene sequences. Larval DNA sequences matched those of syntopic adults of respective species. Detailed descriptionsof external morphology and colouration in life are provided along with ecological notes. The tadpole of R. rufipes and R.dulitensis can be classified as generalized, benthic-nectonic type, whereas tadpoles of R. penanorum show adaptations typical for a lotic, rheophilous lifestyle.

scholarly journals DNA methylation patterns in bacteria of the genus Ensifer during free-living growth and during nitrogen-fixing symbiosis with Medicago spp

2021 ◽  
Author(s):  
George C. diCenzo ◽  
Lisa Cangioli ◽  
Quentin Nicoud ◽  
Janis H.T. Cheng ◽  
Matthew J. Blow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Nitrogen Fixation ◽  
Single Molecule ◽  
Dna Sequences ◽  
Regulatory Mechanism ◽  
Terminal Differentiation ◽  
Nitrogen Fixing ◽  
Genome Wide ◽  
A Genome

ABSTRACTMethylation of specific genomic DNA sequences is ubiquitous in bacteria and has known roles in immunity and regulation of cellular processes, such as the cell cycle. Here, we explored DNA methylation in bacteria of the genus Ensifer, including its potential role in regulating the process of terminal differentiation occurring during nitrogen-fixing symbiosis with legumes. Using single-molecule real-time sequencing, six unique genome-wide methylated motifs were identified across four Ensifer strains, five of which were strain-specific. These five motifs were nearly fully methylated across the genomes in all tested conditions, and they were not enriched in the promoter regions of symbiosis, carbon source, or cell cycle-regulated genes, suggesting that most DNA methylation is not a major regulatory mechanism in the genus Ensifer. Only the GANTC motif, recognized by the cell cycle-regulated CcrM methyltransferase, was methylated in all strains. In actively dividing cells, methylation of GANTC motifs increased progressively from the ori to ter region in each replicon, in agreement with a cell cycle-dependent regulation of CcrM. The GANTC methylation profile transited into a genome-wide pattern of near full methylation in the early stage of symbiotic differentiation, followed by a progressive decrease in methylation from the ori to ter regions of fully differentiated symbiotic bacteria. This is evidence of a dysregulated and constitutive CcrM activity during terminal differentiation, which we suggest is a driving factor for endoreduplication of terminally differentiated bacteroids.IMPORTANCENitrogen fixation by bacteria (rhizobia) in symbiosis with legumes is economically and ecologically important. In some cases, the symbiosis involves a complex bacterial transformation, known as terminal differentiation, that includes major shifts in the transcriptome and cell cycle. Epigenetic regulation via DNA methylation is an important regulatory mechanism contributing to the biology of diverse bacteria; however, the roles of DNA methylation in rhizobia and symbiotic nitrogen fixation have been poorly investigated. We show that aside from cell cycle regulation, DNA methylation is unlikely to be a major mechanism of transcriptional regulation in rhizobia and non-rhizobia of the genus Ensifer. However, we found strong evidence that the cell cycle methyltransferase CcrM is dysregulated during symbiosis, which may be a key factor driving the cell cycle switch in terminal differentiation and the establishment of effective rhizobium – legume symbioses. These novel results advance our understanding of this highly important, yet incompletely understood process.

scholarly journals DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1424 ◽  
Author(s):  
Ordoñez ◽  
Martínez-Calle ◽  
Agirre ◽  
Prosper
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Myeloproliferative Neoplasms ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Specific Gene ◽  
Gene Promoters ◽  
Regulatory Regions ◽  
Genome Wide

Gene regulation through DNA methylation is a well described phenomenon that has a prominent role in physiological and pathological cell-states. This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms.

scholarly journals Relationship of Bacillus amyloliquefaciens clades associated with strains DSM 7T and FZB42T: a proposal for Bacillus amyloliquefaciens subsp. amyloliquefaciens subsp. nov. and Bacillus amyloliquefaciens subsp. plantarum subsp. nov. based on complete genome sequence comparisons

2011 ◽  
Vol 61 (8) ◽  
pp. 1786-1801 ◽  
Author(s):  
Rainer Borriss ◽  
Xiao-Hua Chen ◽  
Christian Rueckert ◽  
Jochen Blom ◽  
Anke Becker ◽  
...  
Keyword(s):  
16S Rrna ◽  
Dna Sequences ◽  
Bacillus Amyloliquefaciens ◽  
Type Strain ◽  
Marker Gene ◽  
Genome Comparison ◽  
Phenotypic Traits ◽  
Whole Genome ◽  
Gene Sequences ◽  
Sequence Comparisons

The whole-genome-sequenced rhizobacterium Bacillus amyloliquefaciens FZB42T (Chen et al., 2007) and other plant-associated strains of the genus Bacillus described as belonging to the species Bacillus amyloliquefaciens or Bacillus subtilis are used commercially to promote the growth and improve the health of crop plants. Previous investigations revealed that a group of strains represented a distinct ecotype related to B. amyloliquefaciens; however, the exact taxonomic position of this group remains elusive (Reva et al., 2004). In the present study, we demonstrated the ability of a group of Bacillus strains closely related to strain FZB42T to colonize Arabidopsis roots. On the basis of their phenotypic traits, the strains were similar to Bacillus amyloliquefaciens DSM 7T but differed considerably from this type strain in the DNA sequences of genes encoding 16S rRNA, gyrase subunit A (gyrA) and histidine kinase (cheA). Phylogenetic analysis performed with partial 16S rRNA, gyrA and cheA gene sequences revealed that the plant-associated strains of the genus Bacillus, including strain FZB42T, formed a lineage, which could be distinguished from the cluster of strains closely related to B. amyloliquefaciens DSM 7T. DNA–DNA hybridizations (DDH) performed with genomic DNA from strains DSM 7T and FZB42T yielded relatedness values of 63.7–71.2 %. Several methods of genomic analysis, such as direct whole-genome comparison, digital DDH and microarray-based comparative genomichybridization (M-CGH) were used as complementary tests. The group of plant-associated strains could be distinguished from strain DSM 7T and the type strain of B. subtilis by differences in the potential to synthesize non-ribosomal lipopeptides and polyketides. Based on the differences found in the marker gene sequences and the whole genomes of these strains, we propose two novel subspecies, designated B. amyloliquefaciens subsp. plantarum subsp. nov., with the type strain FZB42T ( = DSM 23117T = BGSC 10A6T), and B. amyloliquefaciens subsp. amyloliquefaciens subsp. nov., with the type strain DSM 7T( = ATCC 23350T = Fukumoto Strain FT), for plant-associated and non-plant-associated representatives, respecitvely. This is in agreement with results of DDH and M-CGH tests and the MALDI-TOF MS of cellular components, all of which suggested that the ecovars represent two different subspecies.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Monoglobus pectinilyticus gen. nov., sp. nov., a pectinolytic bacterium isolated from human faeces.

2020 ◽  
Author(s):  
CC Kim ◽  
WJ Kelly ◽  
ML Patchett ◽  
GW Tannock ◽  
Z Jordens ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Sequence Similarity ◽  
Middle Lamella ◽  
Rrna Gene ◽  
Gene Sequences ◽  
16S Rrna Gene Sequences ◽  
Citrus Peel ◽  
Human Faeces ◽  
The Family

© 2017 IUMS. A novel anaerobic pectinolytic bacterium (strain 14T) was isolated from human faeces. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 14T belonged to the family Ruminococcaceae, but was located separately from known clostridial clusters within the taxon. The closest cultured relative of strain 14T was Acetivibrio cellulolyticus (89.7% sequence similarity). Strain 14T shared ~99% sequence similarity with cloned 16S rRNA gene sequences from uncultured bacteria derived from the human gut. Cells were Gram-stain-positive, non-motile cocci approximately 0.6μm in diameter. Strain 14T fermented pectins from citrus peel, apple, and kiwifruit as well as carbohydrates that are constituents of pectins and hemicellulose, such as galacturonic acid, xylose, and arabinose. TEM images of strain 14T, cultured in association with plant tissues, suggested extracellular fibrolytic activity associated with the bacterial cells, forming zones of degradation in the pectin-rich regions of middle lamella. Phylogenetic and phenotypic analysis supported the differentiation of strain 14T as a novel genus in the family Ruminococcaceae. The name Monoglobus pectinilyticus gen. nov., sp. nov. is proposed; the type strain is 14T (JCM 31914T=DSM 104782T).

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