ABSTRACT
Key aspects of gene transcription regulation in multicellular organisms, including the characteristics of their promoters, transcription-factor binding sites, and composition elements are reviewed. The functional role of transcription regulatory proteins (basal factors and regulatory transcription factors), and the mechanisms responsible for regulation of their activity are also discussed. Furthermore, we describe the importance of DNA-encoded nucleosome organization and chromatin modifications in the course of transcription regulation, as well as some mechanisms that regulate the activity of transcription factors associated with genetic networks. The current outlook on regulatory gene expression codes in eukaryotes is presented.
Subject(s)
Gene Expression Regulation , Genome , Transcription, Genetic , Animals , Chromatin/metabolism , Eukaryota/genetics , Humans , Nucleosomes/metabolism , Transcription Factors/metabolismABSTRACT
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.
Subject(s)
Computational Biology , Transcription Factors/metabolism , Vertebrates/genetics , Vertebrates/metabolism , Animals , Binding Sites/genetics , Computer Simulation , DNA/genetics , DNA/metabolism , Genome , HumansABSTRACT
The GeneNet system is designed for collection and analysis of the data on gene and metabolic networks, signal transduction pathways and kinetic characteristics of elementary processes. In the past 2 years, the GeneNet structure was considerably improved: (i) the current version of the database is now implemented using ORACLE9i; (ii) the capacities to describe the structure of the protein complexes and the interactions between the units are increased; (iii) two tables with kinetic constants and more detailed descriptions of certain reactions were added; and (iv) a module for kinetic modeling was supplemented. The current SRS release of the GeneNet database contains 37 graphical maps of gene networks, as well as descriptions of 1766 proteins, 1006 genes, 241 small molecules and 3254 relationships between gene network units, and 552 kinetic constants. Information distributed between 16 interlinked tables was obtained by annotating 1980 journal publications. SRS release of the GeneNet database, the graphical viewer and the modeling section are available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/.
Subject(s)
Databases, Genetic , Metabolism , Models, Genetic , Computer Graphics , Computer Simulation , Kinetics , Multiprotein Complexes/chemistry , Signal TransductionABSTRACT
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/.
Subject(s)
Gene Expression Regulation , Systems Integration , Animals , Databases, Genetic , Evolution, Molecular , Promoter Regions, Genetic , RNA, Messenger/genetics , Vertebrates/geneticsABSTRACT
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/.
Subject(s)
Databases, Nucleic Acid , Transcription, Genetic , Animals , Binding Sites , Computer Graphics , DNA-Binding Proteins/metabolism , Gene Silencing , Humans , Information Storage and Retrieval , Internet , Quality Control , Regulatory Sequences, Nucleic Acid , Sequence Homology, Nucleic Acid , Structure-Activity Relationship , Transcription Factors/metabolism , Transcriptional ActivationABSTRACT
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/).
Subject(s)
Databases, Genetic , Metabolism/genetics , Signal Transduction/genetics , Animals , Computer Graphics , Forecasting , Genes , Humans , Information Storage and Retrieval , Internet , Proteins/genetics , Proteins/physiology , RNA/genetics , User-Computer InterfaceABSTRACT
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/
Subject(s)
Databases, Factual , Transcription, Genetic , Enhancer Elements, Genetic , Internet , Promoter Regions, Genetic , Regulatory Sequences, Nucleic AcidABSTRACT
MOTIVATION: 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. RESULTS: 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. AVAILABILITY: 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+ ++.
Subject(s)
Computer Systems , Databases, Factual , Gene Expression , Algorithms , Artificial Intelligence , Base Sequence , Binding Sites/genetics , Chemical Phenomena , Chemistry, Physical , DNA/chemistry , DNA/genetics , DNA/metabolism , Eukaryotic Cells , Internet , Nucleic Acid Conformation , Promoter Regions, Genetic , Protein Biosynthesis , RNA, Messenger/genetics , Software , TATA Box , Transcription Factors/metabolismABSTRACT
SUMMARY: The GeneNet database has been developed for a formalized hierarchical description of the gene networks. To provide rapid data accumulation in the database, the Java graphical interface for data input through the Internet by independent experts equipped with convenient visual tools is developed. AVAILABILITY: http://wwwmgs. bionet.nsc.ru/systems/MGL/GeneNet/
Subject(s)
Databases, Factual , Genes , Computer Graphics , Computer Systems , User-Computer InterfaceABSTRACT
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/
Subject(s)
Databases, Factual , Regulatory Sequences, Nucleic Acid/genetics , Transcription, Genetic/genetics , Animals , Base Sequence , Binding Sites , Cell Line , Databases, Factual/trends , Enhancer Elements, Genetic/genetics , Eukaryotic Cells , Gene Expression Regulation/genetics , Glutathione Peroxidase/genetics , Information Storage and Retrieval , Internet , Mice , Organ Specificity , Promoter Regions, Genetic/genetics , Response Elements/genetics , Russia , Transcription Factors/genetics , User-Computer InterfaceABSTRACT
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.
Subject(s)
Computer Systems , Genes, Regulator , Genome , Artificial Intelligence , Binding Sites , Databases, Factual , Eukaryotic Cells , Gene Expression Regulation , Protein Biosynthesis , RNA, Messenger/genetics , Software , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, GeneticABSTRACT
MOTIVATION: Gene networks that provide the regulation of physiological processes are the basic feature of organisms. Information regarding the regulation of gene expression and signal transduction pathways is increasing rapidly. However, the information is hard to formalize and systematize. Ways and means for automated visualization of the gene networks based on their formalized description are needed. RESULTS: The object-oriented database GeneNet and the software for its automated visualization have been developed. The main principles of a formalized description of the gene network have been worked out. Antiviral response and erythropoiesis are provided as examples to show how this is achieved. The GeneNet graphical user interface written in Java provides automated generation of the gene network diagrams and allows visualization and exploration of the GeneNet database through the Internet. A system of filters allows the selection of particular components of the network for visualization. AVAILABILITY: The GeneNet database and its graphical user interface are available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneN et/ CONTACT: fedor@bionet.nsc.ru
Subject(s)
Databases, Factual , Gene Expression Regulation , Computational Biology , Computer Graphics , Internet , Signal Transduction , Software , User-Computer InterfaceABSTRACT
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
