References of "Ravcheev, Dmitry 50002912"
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See detailComparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus
Rodionov, Dmitry A.; Novichkov, Pavel S.; Stavrovskaya, Elena D. et al

in BMC Genomics (2011), 12 (Suppl 1)(S3), 1-17

BACKGROUND: Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is ... [more ▼]

BACKGROUND: Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. RESULTS: To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR), numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation) and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp). CONCLUSIONS: We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S. oneidensis MR-1. Analysis of correlations in gene expression patterns helps to interpret the reconstructed regulatory network. The inferred regulatory interactions will provide an additional regulatory constrains for an integrated model of metabolism and regulation in S. oneidensis MR-1. [less ▲]

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See detailComparative genomic analysis of the hexuronate metabolism genes and their regulation in gamma-proteobacteria
Suvorova, Inna A.; Tutukina, Maria N.; Ravcheev, Dmitry UL et al

in Journal of Bacteriology (2011), 193(15), 3956-3963

The hexuronate metabolism in Escherichia coli is regulated by two related transcription factors from the FadR subfamily of the GntR family, UxuR and ExuR. UxuR controls the d-glucuronate metabolism, while ... [more ▼]

The hexuronate metabolism in Escherichia coli is regulated by two related transcription factors from the FadR subfamily of the GntR family, UxuR and ExuR. UxuR controls the d-glucuronate metabolism, while ExuR represses genes involved in the metabolism of all hexuronates. We use a comparative genomics approach to reconstruct the hexuronate metabolic pathways and transcriptional regulons in gammaproteobacteria. We demonstrate differences in the binding motifs of UxuR and ExuR, identify new candidate members of the UxuR/ExuR regulons, and describe the links between the UxuR/ExuR regulons and the adjacent regulons UidR, KdgR, and YjjM. We provide experimental evidence that two predicted members of the UxuR regulon, yjjM and yjjN, are the subject of complex regulation by this transcription factor in E. coli. [less ▲]

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See detailInference of the Transcriptional Regulatory Network in Staphylococcus aureus by Integration of Experimental and Genomics-Based Evidence
Ravcheev, Dmitry UL; Best, Aaron A.; Tintle, Nathan et al

in Journal of Bacteriology (2011), 193(12), 3228-3240

Transcriptional regulatory networks are fine-tuned systems that help microorganisms respond to changes in the environment and cell physiological state. We applied the comparative genomics approach ... [more ▼]

Transcriptional regulatory networks are fine-tuned systems that help microorganisms respond to changes in the environment and cell physiological state. We applied the comparative genomics approach implemented in the RegPredict Web server combined with SEED subsystem analysis and available information on known regulatory interactions for regulatory network reconstruction for the human pathogen Staphylococcus aureus and six related species from the family Staphylococcaceae. The resulting reference set of 46 transcription factor regulons contains more than 1,900 binding sites and 2,800 target genes involved in the central metabolism of carbohydrates, amino acids, and fatty acids; respiration; the stress response; metal homeostasis; drug and metal resistance; and virulence. The inferred regulatory network in S. aureus includes ∼320 regulatory interactions between 46 transcription factors and ∼550 candidate target genes comprising 20% of its genome. We predicted ∼170 novel interactions and 24 novel regulons for the control of the central metabolic pathways in S. aureus. The reconstructed regulons are largely variable in the Staphylococcaceae: only 20% of S. aureus regulatory interactions are conserved across all studied genomes. We used a large-scale gene expression data set for S. aureus to assess relationships between the inferred regulons and gene expression patterns. The predicted reference set of regulons is captured within the Staphylococcus collection in the RegPrecise database (http://regprecise.lbl.gov). [less ▲]

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See detailComparative genomics of ethanolamine utilization
Tsoy, Olga; Ravcheev, Dmitry UL; Mushegian, Arcady

in Journal of Bacteriology (2009), 191(23), 7157-7164

Ethanolamine can be used as a source of carbon and nitrogen by phylogenetically diverse bacteria. Ethanolamine-ammonia lyase, the enzyme that breaks ethanolamine into acetaldehyde and ammonia, is encoded ... [more ▼]

Ethanolamine can be used as a source of carbon and nitrogen by phylogenetically diverse bacteria. Ethanolamine-ammonia lyase, the enzyme that breaks ethanolamine into acetaldehyde and ammonia, is encoded by the gene tandem eutBC. Despite extensive studies of ethanolamine utilization in Salmonella enterica serovar Typhimurium, much remains to be learned about EutBC structure and catalytic mechanism, about the evolutionary origin of ethanolamine utilization, and about regulatory links between the metabolism of ethanolamine itself and the ethanolamine-ammonia lyase cofactor adenosylcobalamin. We used computational analysis of sequences, structures, genome contexts, and phylogenies of ethanolamine-ammonia lyases to address these questions and to evaluate recent data-mining studies that have suggested an association between bacterial food poisoning and the diol utilization pathways. We found that EutBC evolution included recruitment of a TIM barrel and a Rossmann fold domain and their fusion to N-terminal alpha-helical domains to give EutB and EutC, respectively. This fusion was followed by recruitment and occasional loss of auxiliary ethanolamine utilization genes in Firmicutes and by several horizontal transfers, most notably from the firmicute stem to the Enterobacteriaceae and from Alphaproteobacteria to Actinobacteria. We identified a conserved DNA motif that likely represents the EutR-binding site and is shared by the ethanolamine and cobalamin operons in several enterobacterial species, suggesting a mechanism for coupling the biosyntheses of apoenzyme and cofactor in these species. Finally, we found that the food poisoning phenotype is associated with the structural components of metabolosome more strongly than with ethanolamine utilization genes or with paralogous propanediol utilization genes per se. [less ▲]

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See detailRegulation of Bacterial Respiration: Comparison of Microarray and Comparative Genomics Data
Tsyganova, M. O.; Gelfand, M. S.; Ravcheev, Dmitry UL

in Molecular Biology (2007), 41(3), 497-512

A comparison was made of the structures of the Fnr and ArcA modulons and regulons. The data on modulon composition were taken from published microarray assays, whereas regulons were characterized using ... [more ▼]

A comparison was made of the structures of the Fnr and ArcA modulons and regulons. The data on modulon composition were taken from published microarray assays, whereas regulons were characterized using comparative genomic approaches. The regulatory cascade involving Fnr and ArcA contributes greatly to the extension of the Fnr modulon over the Fnr regulon by adding operons of the ArcA modulon. The Fnr and ArcA regulons were shown to contain 26 and 16 operons, respectively. Ten operons had high-score and highly conserved sites for both Fnr and ArcA and were isolated as a so-called core of regulons. [less ▲]

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See detailComparative genomic analysis of regulation of anaerobic respiration in ten genomes from three families of gamma-proteobacteria (Enterobacteriaceae, Pasteurellaceae, Vibrionaceae)
Ravcheev, Dmitry UL; Gerasimova, Anna V.; Mironov, Andrey A. et al

in BMC Genomics (2007), 8(54), 1-17

BACKGROUND: Gamma-proteobacteria, such as Escherichia coli, can use a variety of respiratory substrates employing numerous aerobic and anaerobic respiratory systems controlled by multiple transcription ... [more ▼]

BACKGROUND: Gamma-proteobacteria, such as Escherichia coli, can use a variety of respiratory substrates employing numerous aerobic and anaerobic respiratory systems controlled by multiple transcription regulators. Thus, in E. coli, global control of respiration is mediated by four transcription factors, Fnr, ArcA, NarL and NarP. However, in other Gamma-proteobacteria the composition of global respiration regulators may be different. RESULTS: In this study we applied a comparative genomic approach to the analysis of three global regulatory systems, Fnr, ArcA and NarP. These systems were studied in available genomes containing these three regulators, but lacking NarL. So, we considered several representatives of Pasteurellaceae, Vibrionaceae and Yersinia spp. As a result, we identified new regulon members, functioning in respiration, central metabolism (glycolysis, gluconeogenesis, pentose phosphate pathway, citrate cicle, metabolism of pyruvate and lactate), metabolism of carbohydrates and fatty acids, transcriptional regulation and transport, in particular: the ATP synthase operon atpIBEFHAGCD, Na+-exporting NADH dehydrogenase operon nqrABCDEF, the D-amino acids dehydrogenase operon dadAX. Using an extension of the comparative technique, we demonstrated taxon-specific changes in regulatory interactions and predicted taxon-specific regulatory cascades. CONCLUSION: A comparative genomic technique was applied to the analysis of global regulation of respiration in ten gamma-proteobacterial genomes. Three structurally different but functionally related regulatory systems were described. A correlation between the regulon size and the position of a transcription factor in regulatory cascades was observed: regulators with larger regulons tend to occupy top positions in the cascades. On the other hand, there is no obvious link to differences in the species' lifestyles and metabolic capabilities. [less ▲]

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See detailA Gibbs sampler for identification of symmetrically structured, spaced DNA motifs with improved estimation of the signal length
Favorov, A.A.; Gelfand, M.S.; Gerasimova, A.V. et al

in Bioinformatics (2005), 21(10), 2240-2245

Motivation: Transcription regulatory protein factors often bind DNA as homo-dimers or hetero-dimers. Thus they recognize structured DNA motifs that are inverted or direct repeats or spaced motif pairs ... [more ▼]

Motivation: Transcription regulatory protein factors often bind DNA as homo-dimers or hetero-dimers. Thus they recognize structured DNA motifs that are inverted or direct repeats or spaced motif pairs. However, these motifs are often difficult to identify owing to their high divergence. The motif structure included explicitly into the motif recognition algorithm improves recognition efficiency for highly divergent motifs as well as estimation of motif geometric parameters. Result: We present a modification of the Gibbs sampling motif extraction algorithm, SeSiMCMC (Sequence Similarities by Markov Chain Monte Carlo), which finds structured motifs of these types, as well as non-structured motifs, in a set of unaligned DNA sequences. It employs improved estimators of motif and spacer lengths. The probability that a sequence does not contain any motif is accounted for in a rigorous Bayesian manner. We have applied the algorithm to a set of upstream regions of genes from two Escherichia coli regulons involved in respiration. We have demonstrated that accounting for a symmetric motif structure allows the algorithm to identify weak motifs more accurately. In the examples studied, ArcA binding sites were demonstrated to have the structure of a direct spaced repeat, whereas NarP binding sites exhibited the palindromic structure. Availability: The WWW interface of the program, its FreeBSD (4.0) and Windows 32 console executables are available at http://bioinform.genetika.ru/SeSiMCMC [less ▲]

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See detailRegulation of nitrate and nitrite respiration in γ-proteobacteria: a comparative genomics study
Ravcheev, Dmitry UL; Rakhmaninova, A.B.; Mironov, A.A. et al

in Molecular Biology (2005), 39(5), 727-740

Nitrate and nitrite are the most preferable electron acceptors in the absence of molecular oxygen. In the γ-proteobacterium Escherichia coli, nitrate and nitrite respiration is regulated by two homologous ... [more ▼]

Nitrate and nitrite are the most preferable electron acceptors in the absence of molecular oxygen. In the γ-proteobacterium Escherichia coli, nitrate and nitrite respiration is regulated by two homologous tran- scription factors, NarL and NarP. Although this regulatory system was a subject of intensive research for more than 20 years, many key issues, including the structure of the NarL-binding site, are still unclear. Comparative genomics analysis showed that only NarP is responsible for regulation in most γ-proteobacteria. The NarP reg- ulon was studied in ten genomes. Although its structure considerably differs among some genomes, the mech- anism regulating the nitrate and nitrite reduction genes is highly conserved. A correlation was observed between the evolutionary changes in the nitrate and nitrite respiration system and the relevant regulatory system. Poten- tial NarP-binding sites were found upstream of the gene for the global regulator FNR and the sydAB, mdh, and sucAB aerobic metabolism genes. It was assumed on the basis of this evidence that the role of NarP in regulat- ing respiration changed during evolution. In total, 35 new operons were assigned to the generalized NarP reg- ulon. Autoregulation of the narQP operon was suggested for bacteria of the family Vibrionaceae. [less ▲]

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See detailVisualization of individual DNA loops and a map of loop domains in the human dystrophin gene
Iarovaia, Olga V.; Bystritskiy, Andrey; Ravcheev, Dmitry UL et al

in Nucleic Acids Research (2004), 32(7), 2079-2086

The organization of the human dystrophin gene into loop domains has been studied using two different experimental approaches: excision of DNA loops mediated by nuclear matrix-bound topoisomerase II and in ... [more ▼]

The organization of the human dystrophin gene into loop domains has been studied using two different experimental approaches: excision of DNA loops mediated by nuclear matrix-bound topoisomerase II and in situ hybridization of different probes with histone- depleted nuclei (nuclear halos). Our objective was to examine if the DNA loops mapped by this biochemical approach coincide with loops visualized by microscopy. The results obtained using both approaches were in good agreement. Eight loops separated by attachment regions of different length were mapped in the upstream part (up to exon 54) of the gene by topoisomerase II-mediated excision. One of these loops was then directly visualized by in situ hybridization of the corresponding bacmid clone with nuclear halos. This is the ®rst direct demonstration that a DNA domain mapped as a loop using a biochemical approach corresponds to a loop visible on cytological preparations. The validity of this result and of the whole map of loop domains was con®rmed by in situ hybridization using probes derived from other attachment regions or loops mapped by topoisomerase II-mediated cleavage; these probes hybridized on the core or halo region, respectively, of nuclear halos. Our results demonstrate that a single transcription unit may be organized into several loops and that DNA loop attachment regions may be fairly long. Three out of four replication origins mapped in this gene co-localize with loop attachment regions, and the major deletion hot spot is harbored in an attachment region. These results strongly suggest that partitioning of genomic DNA into speci®c loops attached to a skeletal structure is a characteristic feature of eukaryotic chromosome organization in interphase. [less ▲]

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See detailPurine regulon of gamma-proteobacteria: a detailed description
Ravcheev, Dmitry UL; Gelfand, M.S.; Mironov, A.A. et al

in Russian Journal of Genetics (2002), 38(9), 1015-1025

The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhimurium, Yersinia pestis, Haemophilus ... [more ▼]

The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhimurium, Yersinia pestis, Haemophilus influenzae, Pasteurella multocida, Actinobacillus actinomycetemcomitans, and Vibrio cholerae. The palindromic binding site of the purine repressor (consensus ACGCAAACGTTTGCGT) is fairly well conserved upstream genes encoding enzymes that participate in the synthesis of inosine monophosphate from phosphoribozylpyrophosphate and in transfer of one-carbon units, and also upstream of some transport protein genes. These genes may be regarded as the main part of the purine regulon. In terms of physiology, the regulation of the purC and gcvTHP/folD genes seems to be especially important, because the PurR site was found upstream nonorthologous but functionally replaceable genes. However, the PurR site is poorly conserved upstream orthologs of some genes belonging to the E. coli purine regulon, such as genes involved in general nitrogen metabolism, biosynthesis of pyrimidines, and synthesis of AMP and GMP from IMP, and also upstream of the purine repressor gene. It is predicted that purine regulons of the examined bacteria include the following genes: upp participating in synthesis of pyrimidines; uraA encoding an uracil transporter gene; serA involved in serine biosynthesis; folD responsible for the conversion of N5,N10-methenyl tetrahydrofolate into N10-formyltetrahydrofolate; rpiA involved in ribose metabolism; and genes with an unknown function (yhhQ and ydiK). The PurR site was shown to have different structure in different genomes. Thus, the tendency for a decline of the conservatism of site positions 2 and 15 was observed in genomes of bacteria belonging to the Pasteurellaceae and Vibrionaceae groups. [less ▲]

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