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ABSTRACT: Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in
positions −53/−44-and −285/−270 in the promoter region of the mouse Cyp17 gene and in position −117/−108 of the promoter region
of the mouse 3βHSDI gene.
Biochemistry (Moscow) 04/2012; 70(10):1152-1156. · 1.06 Impact Factor
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ABSTRACT: The transcription factor SF-1 (steroidogenic factor 1) regulates the expression of the steroidogenesis genes, coordinates
the development and function of the hypothalamic-pituitary-gonadal and adrenal systems, and plays an important role in the
development and function of the reproductive system. SF-1 belongs to the superfamily of nuclear receptors and activates gene
expression via binding as a monomer to DNA. The SiteGA method was developed for recognizing the binding sites for SF-1. The
method utilizes a genetic algorithm and discriminant analysis to identify the context features of extended (93-bp) regions
harboring the SF-1 sites in a training sample. Recognition of the SF-1 sites showed that the SiteGA method allows more reliable
predictions as compared to the common weight matrix method. Experimental verification of 18 putative SF-1 sites predicted
for the regulatory regions of the steroidogenesis genes showed that 15 (83%) of them did indeed interact with SF-1. The density
of putative SF-1 sites was analyzed in the regulatory regions of genes from various functional groups, and new target genes
of SF-1 were sought in the human genome. The potential targets of SF-1 include the genes coding for cytokine receptors, growth
factor receptors, and proteins involved in the corresponding signal transduction pathways, as well as genes expressed in the
epididymis. Expression of SF-1 in the epididymis was predicted and verified experimentally.
Molecular Biology 04/2012; 40(3):454-464. · 0.66 Impact Factor
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ABSTRACT: The task of automatic extraction of the hierarchical structure of eukaryotic gene regulatory regions is in the junction of the fields of biology, mathematics and information technologies. A solution of the problem involves understanding of sophisticated mechanisms of eukaryotic gene regulation and applying advanced data mining technologies. In the paper the integrated system, implementing a powerful relation mining of biological data method, is discussed. The system allows taking into account prior information about the gene regulatory regions that is known by the biologist, performing the analysis on each hierarchical level, searching for a solution from a simple hypothesis to a complex one. The integration of ExpertDiscovery system into UGENE toolkit provides a convenient environment for conducting complex research and automating the work of a biologist. For demonstration, the system has been applied for recognition of SF1, SREBP, HNF4 vertebrate binding sites and for the analysis the human gene regulatory regions that promote liver-specific transcription.
In silico biology 01/2011; 11(3-4):97-108.
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ABSTRACT: 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 recognition of TFBS, each of which has its own advantages and limitations. A short review of the characteristics of computer methods of TFBS prediction based on various principles is presented. Methods used for experimental monitoring of predicted sites are analyzed. Data concerning DNA regulatory potential and its realization at the chromatin level, obtained using these methods, are discussed along with approaches to recognition of target genes of certain transcription factors in the genome sequences.
Biochemistry (Moscow) 12/2007; 72(11):1187-93. · 1.06 Impact Factor
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[show abstract]
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ABSTRACT: Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in positions -53/-44 and -285/-270 in the promoter region of the mouse Cyp17 gene and in position -117/-108 of the promoter region of the mouse 3betaHSDI gene.
Biochemistry (Moscow) 11/2005; 70(10):1152-6. · 1.06 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in
positions −53/−44-and −285/−270 in the promoter region of the mouse Cyp17 gene and in position −117/−108 of the promoter region
of the mouse 3βHSDI gene.
Biochemistry-moscow - BIOCHEMISTRY-ENGL TR. 01/2005; 70(10):1152-1156.
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ABSTRACT: 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 reflecting molecular mechanisms of interaction. The web resource SITECON is designed to detect conservative conformational and physicochemical properties in transcription factor binding sites, contains a knowledge base of conservative properties for >100 high-quality sample sites and allows for recognition of potential transcription factor binding sites based on conservative properties from both the knowledge base and the results of analysis of a sample proposed by a user. The resource SITECON is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/sitecon/.
Nucleic Acids Research 08/2004; 32(Web Server issue):W208-12. · 8.03 Impact Factor
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N. A. Kolchanov,
O. A. Podkolodnaya,
E. A. Ananko,
D. A. Afonnikov,
O. V. Vishnevsky,
D. G. Vorobiev, E. V. Ignatieva,
V. G. Levitskii,
V. A. Likhoshvai,
N. A. Omelyanchuk,
N. L. Podkolodny,
A. V. Ratushny,
V. V. Suslov
[show abstract]
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ABSTRACT: The review describes several modules of the GeneExpress integrated computer system concerning the regulation of gene expression in eukaryotes. Approaches to the presentation of experimental data in databases are considered. The employment of GeneExpress in computer analysis and modeling of the organization and function of genetic systems is illustrated with examples. GeneExpress is available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/.
Molecular Biology 12/2003; 38(1):58-69. · 0.66 Impact Factor
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ABSTRACT: Using 42 nucleotide sequences extracted from the Transcription Regulatory Regions Database (TRRD) containing SF-1 transcription factor binding site, we have determined the decanucleotide (GTCAAGGTCA) consensus sequence for SF-1 binding. In the frequency matrix of this sequence nucleotides between the 3rd and the 7th position had the highest frequency and guanine nucleotides at the 6th and the 7th positions were recognized in all nucleotide sequences. The latter suggests a crucial role of these guanines for the interaction of DNA with SF-1 protein. The determined consensus and frequency matrix were used for search of putative SF-1 binding sites in regulatory regions of two genes, encoding mouse Cyp17 (17alpha-hydroxylase/17-20-lyase) and 3betaHSDI (3beta-hydroxysteroid dehydrogenase/4delta-5delta-isomerase I), the microsomal enzymes involved in steroidogenesis. 5;-Flanking regions of genes encoding Cyp17 and 3betaHSDI were shown to contain six and five such binding sites, respectively. The presence of the putative SF-1 binding sites in the regulatory regions of mouse Cyp17 and 3betaHSDI suggests that gene SF-1 could represent one of the putative genes which (as we predicted earlier) determine coordinated inheritable variability of hormonal activity in mouse Leydig cells.
Biochemistry (Moscow) 05/2003; 68(4):377-84. · 1.06 Impact Factor
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01/2003; 1(3):142-148.
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ABSTRACT: The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 proteins, 567 genes, 151 other substances and 1364 relationships between components of gene networks. Information distributed between 14 interlinked tables was obtained by annotating 968 scientific publications. The SRS-version of GeneNet database is freely available (http://wwwmgs.bionet.nsc.ru/mgs/systems/genenet/).
Nucleic Acids Research 02/2002; 30(1):398-401. · 8.03 Impact Factor
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ABSTRACT: Transcription Regulatory Regions Database (TRRD) is an informational resource containing an integrated description of the gene transcription regulation. An entry of the database corresponds to a gene and contains the data on localization and functions of the transcription regulatory regions as well as gene expression patterns. TRRD contains only experimental data that are inputted into the database through annotating scientific publication. TRRD release 6.0 comprises the information on 1167 genes, 5537 transcription factor binding sites, 1714 regulatory regions, 14 locus control regions and 5335 expression patterns obtained through annotating 3898 scientific papers. This information is arranged in seven databases: TRRDGENES (general gene description), TRRDLCR (locus control regions); TRRDUNITS (regulatory regions: promoters, enhancers, silencers, etc.), TRRDSITES (transcription factor binding sites), TRRDFACTORS (transcription factors), TRRDEXP (expression patterns) and TRRDBIB (experimental publications). Sequence Retrieval System (SRS) is used as a basic tool for navigating and searching TRRD and integrating it with external informational and software resources. The visualization tool, TRRD Viewer, provides the information representation in a form of maps of gene regulatory regions. The option allowing nucleotide sequences to be searched for according to their homology using BLAST is also included. TRRD is available at http://www.bionet.nsc.ru/trrd/.
Nucleic Acids Research 02/2002; 30(1):312-7. · 8.03 Impact Factor
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ABSTRACT: A complex approach to recognition of transcription factor binding sites (TFBS) has been developed, based on four methods: (i) weight matrix, (ii) information content, (iii) multidimensional alignment, and (iv) pairwise alignment with the most similar representative of known sites. It has been shown that none of the methods considered is optimal for all kinds of sites, so in each case the appropriate way of recognition should be chosen. The approach proposed allows one to minimize the errors in TFBS recognition. The program available through the Internet (http://www.sgi.sscc.ru/mgs/programs/multalig/) has been created to search for the potential TFBS in nucleotide sequences set by the user.
Molecular Biology 10/2001; 35(6):818-825. · 0.66 Impact Factor
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N. A. Kolchanov,
O. A. Podkolodnaya,
E. A. Ananko, E. V. Ignatieva,
N. L. Podkolodnyi,
V. M. Merkulov,
I. L. Stepanenko,
M. A. Pozdnyakov,
O. E. Belova,
D. A. Grigorovich,
A. N. Naumochkin
[show abstract]
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ABSTRACT: The structure of the Transcription Regulatory Regions Database (TRRD) and the principles of describing transcription regulation of eukaryotic genes in TRRD are considered. Formalized description of the structural and functional organization of the regulatory gene regions is illustrated with examples. By now, TRRD is based on 3500 original works and contains data on transcription regulation of more than 1100 genes known to possess more than 5000 transcription factor binding sites and about 1600 regulatory elements (promoters, enhancers, silencers). TRRD is available at http://www.bionet.nsc.ru/trrd/
Molecular Biology 10/2001; 35(6):794-801. · 0.66 Impact Factor
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ABSTRACT: Development of methods for mathematical simulation of biological systems and building specific simulations is an important trend of bioinformatics. Here we describe the method of generalized chemokinetic simulation generating flexible and adequate simulations of various biological systems. Adequate simulations of complex nonlinear gene networks—control system of cholesterol by synthesis in the cell and erythrocyte differentiation and maturation—are given as examples. The simulations were expressed in terms of unit processes—biochemical reactions. Optimal sets of parameters were determined and the systems were numerically simulated under various conditions. The simulations allow us to study the possible functional conditions of these gene networks, calculate the consequences of mutations, and define optimal strategies for their correction including therapeutic ones. A graphical user interface for these simulations is available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneNet/
Molecular Biology 01/2001; 35(6):919-925. · 0.66 Impact Factor
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N A Kolchanov,
O A Podkolodnaya,
E A Ananko, E V Ignatieva,
I L Stepanenko,
O V Kel-Margoulis,
A E Kel,
T I Merkulova,
T N Goryachkovskaya,
T V Busygina,
F A Kolpakov,
N L Podkolodny,
A N Naumochkin,
I M Korostishevskaya,
A G Romashchenko,
G C Overton
[show abstract]
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ABSTRACT: Transcription Regulatory Regions Database (TRRD) has been developed for accumulation of experimental information on the structure-function features of regulatory regions of eukaryotic genes. Each entry in TRRD corresponds to a particular gene and contains a description of structure-function features of its regulatory regions (transcription factor binding sites, promoters, enhancers, silencers, etc.) and gene expression regulation patterns. The current release, TRRD 4.2.5, comprises the description of 760 genes, 3403 expression patterns, and >4600 regulatory elements including 3604 transcription factor binding sites, 600 promoters and 152 enhancers. This information was obtained through annotation of 2537 scientific publications. TRRD 4.2.5 is available through the WWW at http://wwwmgs.bionet.nsc.ru/mgs/dbases/trrd4/
Nucleic Acids Research 02/2000; 28(1):298-301. · 8.03 Impact Factor
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N A Kolchanov,
M P Ponomarenko,
A S Frolov,
E A Ananko,
F A Kolpakov, E V Ignatieva,
O A Podkolodnaya,
T N Goryachkovskaya,
I L Stepanenko,
T I Merkulova, [......],
A V Kochetov,
N L Podkolodny,
D V Vorobiev,
S V Lavryushev,
D A Grigorovich,
Y V Kondrakhin,
L Milanesi,
E Wingender,
V Solovyev,
G C Overton
[show abstract]
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ABSTRACT: The goal of the work was to develop a WWW-oriented computer system providing a maximal integration of informational and software resources on the regulation of gene expression and navigation through them. Rapid growth of the variety and volume of information accumulated in the databases on regulation of gene expression necessarily requires the development of computer systems for automated discovery of the knowledge that can be further used for analysis of regulatory genomic sequences.
The GeneExpress system developed includes the following major informational and software modules: (1) Transcription Regulation (TRRD) module, which contains the databases on transcription regulatory regions of eukaryotic genes and TRRD Viewer for data visualization; (2) Site Activity Prediction (ACTIVITY), the module for analysis of functional site activity and its prediction; (3) Site Recognition module, which comprises (a) B-DNA-VIDEO system for detecting the conformational and physicochemical properties of DNA sites significant for their recognition, (b) Consensus and Weight Matrices (ConsFrec) and (c) Transcription Factor Binding Sites Recognition (TFBSR) systems for detecting conservative contextual regions of functional sites and their recognition; (4) Gene Networks (GeneNet), which contains an object-oriented database accumulating the data on gene networks and signal transduction pathways, and the Java-based Viewer for exploration and visualization of the GeneNet information; (5) mRNA Translation (Leader mRNA), designed to analyze structural and contextual properties of mRNA 5'-untranslated regions (5'-UTRs) and predict their translation efficiency; (6) other program modules designed to study the structure-function organization of regulatory genomic sequences and regulatory proteins.
GeneExpress is available at http://wwwmgs.bionet.nsc. ru/systems/GeneExpress/ and the links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.
Bioinformatics 09/1999; 15(7-8):669-86. · 5.47 Impact Factor
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N A Kolchanov,
E A Ananko,
O A Podkolodnaya, E V Ignatieva,
I L Stepanenko,
O V Kel-Margoulis,
A E Kel,
T I Merkulova,
T N Goryachkovskaya,
T V Busygina,
F A Kolpakov,
N L Podkolodny,
A N Naumochkin,
A G Romashchenko
[show abstract]
[hide abstract]
ABSTRACT: The Transcription Regulatory Regions Database (TRRD) is a curated database designed for accumulation of experimental data on extended regulatory regions of eukaryotic genes, the regulatory elements they contain, i.e., transcription factor binding sites, promoters, enhancers, silencers, etc., and expression patterns of the genes. Release 4.1 of TRRD offers a number of significant improvements, in particular, a more detailed description of transcription factor binding sites, transcription factors per se, and gene expression patterns in a computer-readable format. In addition, the new TRRD release provides considerably more references to other molecular biological databases. TRRD 4.1 is installed under SRS and is available through the WWW at http://www.bionet.nsc.ru/trrd/
Nucleic Acids Research 02/1999; 27(1):303-6. · 8.03 Impact Factor
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N A Kolchanov,
M P Ponomarenko,
A E Kel,
Kondrakhin YuV,
A S Frolov,
F A Kolpakov,
T N Goryachkovsky,
O V Kel,
E A Ananko, E V Ignatieva, [......],
D G Vorobiev,
S V Lavryushev,
Ponomarenko YuV,
A V Kochetov,
G B Kolesov,
V V Solovyev,
L Milanesi,
N L Podkolodny,
E Wingender,
T Heinemeyer
[show abstract]
[hide abstract]
ABSTRACT: GeneExpress system has been designed to integrate description, analysis, and recognition of eukaryotic regulatory sequences. The system includes 5 basic units: (1) GeneNet contains an object-oriented database for accumulation of data on gene networks and signal transduction pathways and a Java-based viewer that allows an exploration and visualization of the GeneNet information; (2) Transcription Regulation combines the database on transcription regulatory regions of eukaryotic genes (TRRD) and TRRD Viewer; (3) Transcription Factor Binding Site Recognition contains a compilation of transcription factor binding sites (TFBSC) and programs for their analysis and recognition; (4) mRNA Translation is designed for analysis of structural and contextual features of mRNA 5'UTRs and prediction of their translation efficiency; and (5) ACTIVITY is the module for analysis and site activity prediction of a given nucleotide sequence. Integration of the databases in the GeneExpress is based on the Sequence Retrieval System (SRS) created in the European Bioinformatics Institute.
Proceedings / ... International Conference on Intelligent Systems for Molecular Biology; ISMB. International Conference on Intelligent Systems for Molecular Biology 02/1998; 6:95-104.
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T Heinemeyer,
E Wingender,
I Reuter,
H Hermjakob,
A E Kel,
O V Kel, E V Ignatieva,
E A Ananko,
O A Podkolodnaya,
F A Kolpakov,
N L Podkolodny,
N A Kolchanov
[show abstract]
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ABSTRACT: TRANSFAC, TRRD (Transcription Regulatory Region Database) and COMPEL are databases which store information about transcriptional regulation in eukaryotic cells. The three databases provide distinct views on the components involved in transcription: transcription factors and their binding sites and binding profiles (TRANSFAC), the regulatory hierarchy of whole genes (TRRD), and the structural and functional properties of composite elements (COMPEL). The quantitative and qualitative changes of all three databases and connected programs are described. The databases are accessible via WWW:http://transfac.gbf.de/TRANSFAC orhttp://www.bionet.nsc.ru/TRRD
Nucleic Acids Research 02/1998; 26(1):362-7. · 8.03 Impact Factor
