Dmitry Oshchepkov

Russian Academy of Sciences | RAS · Institute of Cytology and Genetics, Siberian Branch

Studies on hereditary fixation of the tame-behavior phenotype during animal domestication remain relevant and important because they are of both basic research and applied significance. In model animals, gray rats Rattus norvegicus bred for either an enhancement or reduction in defensive response to humans, for the first time, we used high-throughp...

Although half of hypertensive patients have hypertensive parents, known hypertension-related human loci identified by genome-wide analysis explain only 3% of hypertension heredity. Therefore, mainstream transcriptome profiling of hypertensive subjects addresses differentially expressed genes (DEGs) specific to gender, age, and comorbidities in acco...

Belyaev’s concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before hu...

Using our previously published Web service SNP_TATA_Comparator, we conducted a genome-wide study of single-nucleotide polymorphisms (SNPs) within core promoters of 68 human rheumatoid arthritis (RA)-related genes. Using 603 SNPs within 25 genes clinically associated with RA-comorbid disorders, we predicted 84 and 70 candidate SNP markers for overex...

Earlier, after our bioinformatic analysis of single-nucleotide polymorphisms of TATA-binding protein-binding sites within gene promoters on the human Y chromosome, we suggested that human reproductive potential diminishes during self-domestication. Here, we implemented bioinformatics models of human diseases using animal in vivo genome-wide RNA-Seq...

A new structural variant of the transcription factor EIN3 binding site has been obtained. This structural variant is strongly associated with the transcriptional response to ethylene and is preferred for EIN3 binding. Based on this structural variant, a new genetic ethylene sensor was developed.

Abstract Background In population ecology, the concept of reproductive potential denotes the most vital indicator of chances to produce and sustain a healthy descendant until his/her reproductive maturity under the best conditions. This concept links quality of life and longevity of an individual with disease susceptibilities encoded by his/her gen...

(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. (2) Methods: We applied the motifs co-occurrence too...

Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. Methods: We applied Motifs Co-Occurrence Tool (MCOT) tha...

Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. Methods: We applied Motifs Co-Occurrence Tool (MCOT) tha...

(1) Background: The World Health Organization (WHO) regards atherosclerosis-related myocardial infarction and stroke as the main causes of death in humans. Susceptibility to atherogenesis-associated diseases is caused by single-nucleotide polymorphisms (SNPs). (2) Methods: Using our previously developed public web-service SNP_TATA_Comparator, we es...

Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been conducted on animals rather than humans. Recently,...

Recognition of composite elements consisting of two transcription factor binding sites gets behind the studies of tissue-, stage-and condition-specific transcription. Genome-wide data on transcription factor binding generated with ChIP-seq method facilitate an identification of composite elements, but the existing bioinformatics tools either requir...

Complete list of differentially expressed genes.

Schematic components of a continuous culture bioreactor. MTU-Mass Transfer Unit; MSP-Manual Sample Port; MFM-Mass Flow Meter;BS-Bluesens sensors. The protocol is adapted for working with a mini-parallel bioreactor system, such as DasBox (Eppendorf). The system is connected to a custom-built gas-distribution system, which controls the gas-mixture in...

(A) Principal component analysis of analyzed transcriptomic datasets. Individual samples are indicated according to the next notation: light red circle – Ca-regulated growth, blue circle – La-regulated growth; (B) The MA-plot shows the log2 fold changes between Ca- and La-regulated growths of 20 Z over the mean of normalized counts. The x-axis repr...

Three-spine stickleback (Gasterosteus aculeatus) is a well-known model organism that is routinely used to explore microevolution processes and speciation, and the number of studies related to this fish has been growing recently. The main reason for the increased interest is the processes of freshwater adaptation taking place in natural populations...

Трехиглая колюшка (Gasterosteus aculeatus) является удобным объектом для изучения эволюции и процессов видообразования. Количество исследований с ее участием в последние годы неуклонно растет, что обусловлено процессами образования пресноводных форм у данного вида, которые происходят в настоящее время. Морская форма этого вида, заходя на нерест в п...

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is involved in a wide range of critical cellular events in response to endogenous signals or xenobiotics. 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) is one of the AhR ligands with the maximum affinity for AhR. TCDD is the most toxic among the dioxin xenobiotics and ind...

The plant hormone ethylene regulates numerous developmental processes and stress responses. Ethylene signaling proceeds via a linear pathway, which activates transcription factor (TF) EIN3, a primary transcriptional regulator of ethylene response. EIN3 influences gene expression upon binding to a specific sequence in gene promoters. This interactio...

Steroidogenic factor 1 (SF-1) belongs to a small group of the transcription factors that bind DNA only as a monomer. Three different approaches—Sitecon, SiteGA, and oPWM—constructed using the same training sample of experimentally confirmed SF-1 binding sites have been used to recognize these sites. The appropriate prediction thresholds for recogni...

The aryl hydrocarbon receptor (AhR), a ligand- activated transcription factor, participates in a wide range of critical cellular events in response to endogenous signals or xenobiotic chemicals. 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is one of the AhR ligands with a very high binding affinity for the AhR. TCDD is the most toxic among the dio...

Nonthermal effects of terahertz radiation on living objects are currently intensely studied, as more sources of this radiation type and devices employing it are being constructed. Terahertz radiation is increasingly used in security and inspection systems, medical and scientific appliances due to its low quant energy, which does not cause severe ef...

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic among the dioxin xenobiotics and induces a broad spectrum of biological responses, including immunotoxicity and cancer [1]. Macrophages are very plastic cells and can acquire various functionally distinct phenotypes depending on the physiological context. They...

The development of in vitro technologies has produced new experimental information on protein binding onto DNA, which is accumulated in databases and used in studies of mechanisms regulating gene expression and in the development of computer-assisted methods of binding site recognition in pro- and eukaryotic genomes. However, it is still questionab...

Mechanisms governing the expression of the dps gene with the presence of cadmium ions have been reconstructed from the dynamics of the fluorescence of a genosensor construct with the dps promoter of Escherichia coli and the gfp reporter gene. Mathematical modeling and bioinformational analysis have been invoked. Estimation of the consistence of var...

Interleukin IL-12 is a key proinflammatory cytokine synthesized by macrophages; however, information on the effect of dioxin on its expression is still fragmentary. The presence of previously identified potential dioxin-responsive elements (DREs) in the regulatory regions of IL12A and IL12B genes, encoding IL-12 subunits IL-12p35 and IL-12p40, resp...

ChIP-Seq is widely used to detect genomic segments bound by transcription factors (TF), either directly at DNA binding sites (BSs) or indirectly via other proteins. Currently, there are many software tools implementing different approaches to identify TFBSs within ChIP-Seq peaks. However, their use for the interpretation of ChIP-Seq data is usually...

The regulatory region of the Escherichia coli yfiA gene was reconstructed by using the SITECON web resource and mathematical modeling; the complexity of its expression under oxidative stress was assessed. Simulation of the response of E. coli cells transformed with the pYfi-gfp plasmid to oxidative stress indicated that the maximum agreement with e...

Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) became a method of choice to locate DNA segments bound by different regulatory proteins. ChIP-Seq produces extremely valuable information to study transcriptional regulation. The wet-lab workflow is often supported by downstream computational analysis including construction of mod...

Identification and consequent analysis of DNA sequence motifs recognized by transcription factors is an important component in studying transcriptional regulation in higher eukaryotes. In particular, motif discovery methods are applied to construct transcription factor binding sites (TFBSs) models. The TFBS models are then used for prediction of pu...

The pilot program complex for analysis of symbol sequences in genomics, ICGenomics, has been designed for storage, mining, and analysis of sequences related to theoretical and applied genomics. ICGenomics enables wet-lab biologists to perform high-quality processing of data in the fields of genomics, biomedicine, and biotechnology. ICGenomics imple...

The transcription factor GAGA, encoded by the gene Trl, controls expression of many Drosophila melanogaster genes. We have compiled the presently largest sample (120 sites) of published nucleotide sequences with experimentally confirmed binding to GAGA protein. Analysis of the sample has demonstrated that despite an apparent structural diversity of...

The recognition of transcription factor binding sites (TFBSs) is the first step on the way to deciphering the DNA regulatory code. A large variety of computational approaches and corresponding in silico tools for TFBS recognition are available, each having their own advantages and shortcomings. This chapter provides a brief tutorial to assist end u...

Chromatin immunoprecipitation followed by mass parallel sequencing of the precipitated fragments (ChIP-Seq) is broadly used for detailed investigation of the distribution of various transcription factor binding sites over the whole genome. The ChIP-Seq profiles obtained by immunoprecipitation of mouse liver chromatin with antibodies against the Fox...

The computer system SITECON was used to study the regulatory regions in the transcription factor genes expressed in the activated macrophage and the genes of the proteins mediating the macrophage involvement in the immune response. Dioxin responsive elements (DREs), the specific sites responsible for expression regulation of the genes involved in t...

Earlier we discovered transactivation of the HIV-1 and hepatitis B virus (HBV) in human cells by 30-300 ppt dioxin, a xenobiotic with extremely long serum half-life in humans. Also, upregulation of cytomegalovirus (HCMV) in human cells was shown by 10 ppq dioxin whereas current its background level in general population is ~4 ppt. So, human viruses...

Here, we propose with regard to proinflammatory and premalignancy cytokines that their AhR-mediated regulation by TCDD in macrophages might be executed by a dual mechanism: direct interaction of TCDD (at nanomolar concentrations) with promoter DRE of ultimate cytokine gene, and throughout a cascade of interrelated genes. The latter is epitomized by...

Here, we propose with regard to proinflammatory and premalignancy cytokines that their AhR-mediated regulation by TCDD in macrophages might be executed by a dual mechanism: direct interaction of TCDD (at nanomolar concentrations) with promoter DRE of ultimate cytokine gene, and throughout a cascade of interrelated genes. The latter is epitomized by...

To reveal the mechanism of tumor-suppressing activity of FOXA proteins in liver, a search for potential target genes of these transcription factors involved in proliferation control was carried out. In the first step, we have used data from the literature concerning gene expression in mouse liver (high content of FOXA proteins) and kidney (FOXA exp...

Insulin is the important regulator of adipose cell metabolism and activates the branched out network of the signaling pathways supervising glucose transport, glycogen synthesis, lipogenesis stimulation, lipolysis inhibition and adipokine secretion. The purpose of our work is the analysis of structure of regulatory contours providing the response of...

The development of computer-assisted methods for transcription factor binding sites (TFBS) recognition is necessary for study the DNA regulatory transcription code. There are a great number of experimental methods that enable TFBS identification in genome sequences. The experimental data can be used to elaborate multiple computer approaches to reco...

Organohalogen Compounds, volume 69 (2), pp. 1889-1894 (2007) A computational search for dioxin responsive elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by SITECON. This tool efficiently detected all proved functional DREs in human CYP1A1, CYP1B1, and rat epiregulin genes. Eventually, the...

ORGANOHALOGEN COMPOUNDS Journal, volume 69:1889-1894 (2007). ABSTRACT: A computational search for dioxin responsive elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by SITECON. This tool efficiently detected all proved functional DREs in human CYP1A1, CYP1B1, and rat epiregulin genes. Eventu...

The recognition of transcription factor binding sites (TFBSs) is the first step on the way to deciphering the DNA regulatory code. There is a large variety of experimental approaches providing information on TFBS location in genomic sequences. Many computational approaches to TFBS recognition based on the experimental data obtained are available, e...

Human gene RFP2 is a candidate tumor suppressor located at 13q14.3 and deleted in multiple tumor types. To explore regulation of RFP2, we determined structure of the 5'-untranslated region of RFP2 gene and its promoter. RFP2 promoter area is TATA-less, highly enriched in G and C nucleotides, and contains multiple quadruplex forming GGGGA-repeats. D...

Epstein-Barr virus (EBV) is a common herpes virus that establishes a life long persistence in the human host and can directly transform B lymphocytes. EBV can drive B cell development and survival in the absence of normal B cell receptor signals. The goal of our work was to define the mechanisms by which EBV regulates B cell fate. We developed new...

The structure-forming function of alpha satellites in arrangement of the centromeric heterochromatin implies the presence of certain contextual and conformational signals (codes) for compacting DNA of these regions into nucleosomes and chromatin structures of higher level. However, this aspect of informational content of alpha satellite primary DNA...

The ArtSite database was developed; the database compiles the information on the structures of eukaryotic transcription factor binding sites and/or their DNA-binding domains obtained from in vitro selected sequences. Current release of the database comprises 420 matrices describing specific features of binding sites or their DNA-binding domains for...

DNA binding with enzymes is followed by specific adaptation of the DNA structure, including partial or almost complete melting, structural changes in the sugar-phosphate backbone, stretching, compressing, bending or kinking, base flipping, etc. The set of conformational changes is individual for each enzyme and is aimed at efficiently adjusting the...

After complexation of DNA with enzymes a specific adaptation of DNA structure including its partial or nearly complete melting, change of sugar-phosphate backbone structure, stretching, compression, bending or kinking, flipping out of nucleotides from the DNA helix, etc. take place. The full set of such changes is specific for each individual enzym...

The local DNA conformation in the region of transcription factor binding sites, determined by context, is one of the factors underlying the specificity of DNA–protein interactions. Analysis of the local conformation of a set of functional DNA sequences may allow for determination of the conservative conformational and physicochemical parameters ref...

Research into molecular mechanisms underlying DNA-protein interactions using statistical analysis of nucleotide sequences of binding sites is most important for understanding the principles of gene expression regulation. The local conformation of transcription factor binding sites determined by their context is a factor responsible for specificity...

Annotation of scientific papers using the GeneNet technology allowed for reconstruction of the gene network regulating the cell cycle (the G1/S transition). To extend the network, we searched for potential sites for E2F transcription factor binding in promoter regions of genes whose expression depends on the cell cycle phase, however, any experimen...

We applied in silico methods to analyze contextual and structural characteristics of Drosophila DNA in the regions of insertions of LTR retrotransposons belonging to 12 families, namely, 17.6, 297, blood, copia, Dm412 (mdg2), gypsy, HMSBeagle, mdgl, mdg3, roo (B104), tirant, and yoyo, and to detect the properties that might determine why these regi...

Resume Motivation: A rapid discovering of experimental data on regulation of gene expression and their accumulation in various databases accompanied by development of numerous and diverse software tools for their analyses demands integration of the available informational and software resources. Results: An Internet-accessible system GeneExpress-2....

Key words: conformational and physicochemical DNA properties, DNA-protein interactions, parameters of DNA recognized by human DNA topoisomerase I Resume Motivation: DNA topoisomerase I (topo) is a sequence-specific enzyme; however, it is able to cleave DNA sequences differing from the optimal sequence with lower efficiency. The sequence and, conseq...

It is known that the physico-chemical characteristics of proteins underlying specific folding of the polypeptide chain and the protein function are evolutionary conserved. Detection of such characteristics while analyzing homologous sequences would expand essentially the knowledge on protein function, structure, and evolution. These characteristics...

Resume Motivation: Typical of topoisomerase I (topo I) cleavage sites are lack of consensus. Therefore, the conformational characteristics of the DNA helix might play the key role in determining the cleavage sites. Results: Correlation analysis of DNA conformational characteristics of human topo I cleavage sites has discovered the characteristics o...

SUMMARY Motivation: It is of great importance to keep studying lipid metabolism regulation in the adipose tissue, because the tissue excess is a risk factor for serious human diseases (dyslipidemia, diabetes, cardiovascular ones). This is why the accumulation and analysis of data on the regulation of the expression of adipocyte genes are expected t...

Motivation: Considerable increases in the transposition rate of Drosophila retrotransposons under the effect of various stress factors, in particular, heat shock, have been described. The proposed interpretation of this phenomenon (heat shockactivated transcription) as well as the question on whether the observed changes in retrotransposon distribu...

Key words: site recognition, conformational and physicochemical DNA properties, DNA-protein interactions, transcription factor Motivation: The local conformation of transcription factor binding sites resulting from their contexts is a factor determining the specificity of DNA-protein interactions. A set of conservative conformational and physicoche...

Motivation: Disruption of lipid metabolism is known to cause a set of severe human diseases. Transcription factor SREBP (Sterol Regulatory Element Binding Protein) is a key regulator of cholesterol homeostasis gene expression, hence, analysis of SREBP binding site data, as well as development of a reliable method for SREBP binding sites recognition...