Papers by Edgar Wingender
Advances in experimental medicine and biology, 1997
The structure of the RT6 mono(ADP-ribosyl)transferase gene was studied. Analysis of cDNA clones r... more The structure of the RT6 mono(ADP-ribosyl)transferase gene was studied. Analysis of cDNA clones revealed eight exons and suggested two independent transcriptional start sites. The existence of the downstream initiation site was confirmed by S1-nuclease protection and localized to position +29 of exon 2. The corresponding 5' flanking regions were found to contain typical promoter structures such as TATA- and CCAAT-boxes. Comparison with sequences deposited in the TRANSFAC database of transcription factor binding sites revealed few putative regulatory elements in the region associated with exon 1 (promoter 1). In contrast, several elements contained in the regulatory regions of other T cell-specific genes, such as ets, lyf-1 and ikaros were found in in promoter 2. Analysis of RT6-transcripts showed this region to be the most active promoter in spleen cells of adult rats. Finally, transient transfection assays with reporter gene constructs showed promoter 2 to mediate T-cell specif...
Journal of immunology (Baltimore, Md. : 1950), 1996
Cellular functions, such as the cytolytic potential of CTLs, can be regulated by mono-ADP-ribosyl... more Cellular functions, such as the cytolytic potential of CTLs, can be regulated by mono-ADP-ribosylation of target proteins. Recently, the T cell differentiation marker RT6 has been shown to possess mono-ADP-ribosyltransferase activity. Defects in RT6 expression coincide with increased susceptibility in animal models for insulin-dependent diabetes mellitus and other autoimmune diseases. We present an analysis of the rat RT6 gene, providing a basis for studying the regulation of this gene in T cells of normal and diabetes-prone rats. It is the first structural analysis of a mammalian mono-ADP-ribosyltransferase gene. The RT6 gene consists of eight exons spanning approximately 20 kb. The proximal four exons encode 5' untranslated region sequences and are found in multiple alternatively spliced variants. Exon 5 encodes the N-terminal signal sequence. An unusually large exon 7 encodes the entire native polypeptide. The final exon 8 encodes the C-terminal signal sequence for glycosylph...
This investigation presents the structural changes in condylar cartilage incubated in the presenc... more This investigation presents the structural changes in condylar cartilage incubated in the presence of human parathyroid hormone (1-34) in an organ culture system for 6 to 12 days. Control cultures maintained their cartilaginous characteristics whereas human parathyroid hormone (1-34)-treated cultures revealed the following modifications: (1) The chondroprogenitor cell zone at the apical region of the explant underwent a substantial enlargement. The cells changed from a mesenchyme-like morphology into polygonal, glycogen-rich cells that were tightly attached to each other by a fibrillar intercellular matrix, but even by 12 days the apical region was comprised of healthy cells. (2) The mineralizing zone in the hypertrophic cartilage revealed a change in its cellular population. Hypertrophic chondrocytes were replaced by cells with amoeboid extensions and large numbers of secretory granules or vesicles. Based upon the above findings it appears that the condroprogenitor cells that are initially stimulated to proliferate, are being suppressed from subsequent differentiation into chondroblasts; and that hypertrophic chondrocytes apparently undergo a dedifferentiation process followed by development into an as yet unknown cell population.
Trends in Plant Science, 2001
Handbook of Plant Biotechnology, 2004
PLoS ONE, 2011
The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malign... more The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.
Nature Biotechnology, 2010
ABSTRACT p e r s p e c t i v e Biological Pathway Exchange (BioPAX) is a standard language to rep... more ABSTRACT p e r s p e c t i v e Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery. Increasingly powerful technologies, including genome-wide molecular measurements, have accelerated progress toward a complete map of molecular interaction networks in cells and between cells of many organ-isms. The growing scale of these maps requires their representation in a form suitable for computer processing, storage and dissemination by means of software systems. The BioPAX project aims to facilitate knowledge representation, systematic collection, integration and wide distribution of pathway data from heterogeneous information sources. This will enable these data to be incorporated into distributed biological information systems that support visualization and analysis. BioPAX supports efforts working toward a complete representa-tion of basic cellular processes. Biology has come a long way since the Boehringer-Mannheim wall chart of metabolic pathways 1 and the Nicholson Metabolic Map 2 . Since then, several groups have developed methods and databases for organizing pathway information 3–16 , but only recently have groups collaborated as part of the BioPAX project to develop a generally accepted standard way of representing these pathway maps. Complete molecular process maps must include all interactions, reactions, dependencies, influence and information flow between pools of molecules in cells and between cells. For ease of use and simplicity of presentation, such network maps are often organized in terms of subnetworks or pathways. Pathways are models delineated within the entire cellular biochemical network that help us describe and understand specific biological processes. Thus, a useful definition of a pathway is a set of interactions between physical or genetic cell compo-nents, often describing a cause-and-effect or time-dependent process, that explains observable biological phenomena. How do we represent these pathways in a generally accepted and computable form? Challenges posed by the many fragmented pathway databases The total volume of pathway data mapped by biologists and stored in databases has entered a rapid growth phase, with the number of
Bioinformatics, 1999
The goal of the work was to develop a WWW-oriented computer system providing a maximal integratio... more 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 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; 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 Contact: [email protected] Vol. 15 nos 7/8 1999 Pages 669-686 669 E Oxford University Press 1999 BIOINFORMATICS N.A.Kolchanov et al.
Biochemistry, 1991
The structure of human parathyroid hormone fragment (1-34) in a solvent mixture of water and trif... more The structure of human parathyroid hormone fragment (1-34) in a solvent mixture of water and trifluoroethanol has been determined by 1H nuclear magnetic resonance spectroscopy and a combination of distance geometry and molecular dynamic simulations. After complete assignment of the 1H signals, the nuclear Overhauser enhancement data imply the existence of two alpha-helices, comprising residues 3-9 and 17-28, joined by a nonstructured region. The absence of any long-range NOEs and the relative magnitudes of the sequential NOEs and the 3J(HNH alpha) values reflect an inherent flexibility within the entire fragment. The final structures refined by molecular dynamics further support the above results and allow discussion of structural-activity relationships.
Series on Advances in Bioinformatics and Computational Biology, 2005
Frontiers in genetics, 2012
The semantic web depends on the use of ontologies to let electronic systems interpret contextual ... more The semantic web depends on the use of ontologies to let electronic systems interpret contextual information. Optimally, the handling and access of ontologies should be completely transparent to the user. As a means to this end, we have developed a service that attempts to bridge the gap between experts in a certain knowledge domain, ontologists, and application developers. The ontology-based answers (OBA) service introduced here can be embedded into custom applications to grant access to the classes of ontologies and their relations as most important structural features as well as to information encoded in the relations between ontology classes. Thus computational biologists can benefit from ontologies without detailed knowledge about the respective ontology. The content of ontologies is mapped to a graph of connected objects which is compatible to the object-oriented programming style in Java. Semantic functions implement knowledge about the complex semantics of an ontology beyond...
Theoretical biology & medical modelling, 2005
Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and betw... more Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. P. aeruginosa is a pathogen that causes acute and chronic lung infections by interacting with the pulmonary epithelial cells. We use this example for examining the ways of triggering the response of the eukaryotic cell(s), leading us to a better understanding of the details of the inflammatory process in general. Considering a set of genes co-expressed during the antibacterial response of human lung epithelial cells, we constructed a promoter model for the search of additional target genes potentially involved in the same cell response. The model construction is based on the consideration of pair-wise combinations of transcription factor binding sites (TFBS). It has been shown that the antibacterial response of human epithelial cells is triggered by at least two distinct pathways. We therefore supposed that there are two subsets of promoters activated by each of them. Opt...
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 1997
The TRANSFAC database contains information about regulatory DNA sequences and the proteins (trans... more The TRANSFAC database contains information about regulatory DNA sequences and the proteins (transcription factors) binding to and acting through them. It may thus serve as a dictionary for the biological meaning of these sequence elements. Moreover, the TRANSFAC data can be used to describe these elements, to define consensi and matrices for elements of certain function, and thus to provide means of identifying regulatory signals in newly unravelled genomic sequences.
Molekuliarnaia biologiia
We have developed a method for revealing local conformation properties of binding sites for trans... more We have developed a method for revealing local conformation properties of binding sites for transcription factors, based on conformation indices of B-sheet DNA hexanucleotide duplexes and computer system SITEVIDEO. Analysis of sequences with TATA box has revealed the promoter regions with certain conformation indices of B-sheet DNA significantly changed as compared with arbitrary sequences: TATA-box DNA has a lower angle of helical twist, smaller distance between neighbor base pairs along the DNA helix axis, wider minor and narrower major DNA grooves.
Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology, 1995
We present the computer tool FUNSITE for description and analysis of regulatory sequences of euka... more We present the computer tool FUNSITE for description and analysis of regulatory sequences of eukaryotic genomes. The tool consists of the following main parts: 1) An integrated database for genomic regulatory sequences. The integrated database was designed on the basis of the databases TRANSFAC (Wingender 1994) and TRRD (Kel et al. 1995) that are currently under development. The following functions are performed: i) linkage to the EMBL database; ii) preparing samples of definite types of functional sites with their flanking sequences; iii) preparing samples of promoter sequences; iv) preparing samples of transcription factors classified with regard to structural and functional features of DNA binding and activating domains, functional families of the factors, their tissue specificity and other functional features; v) access to data on mutual disposition of cis-elements within the regulatory regions. 2) The second component of FUNSITE tool is the set of programs for analysis of the s...
The Biochemical journal, Jan 15, 1990
We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimula... more We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimulate creatine kinase (CK) activity and [3H]thymidine incorporation into DNA via phosphoinositide turnover, in addition to its other actions via increased cyclic AMP production. We also found that mid-region fragments of PTH stimulate [3H]thymidine incorporation into avian chondrocytes. In the present study of mammalian systems, we demonstrate differential effects of defined synthetic PTH fragments on CK activity and DNA synthesis, as compared with cyclic AMP production, in osteoblast-enriched embryonic rat calvaria cell cultures, in an osteoblast-like clone of rat osteosarcoma cells (ROS 17/2.8) and in chondroblasts from rat epiphysial cartilage cell cultures. Unlike full-length bovine (b)PTH-(1-84) or the fully effective shorter fragment human (h)PTH-(1-34), fragments lacking the N-terminal region of the hormone did not increase cyclic AMP formation, whereas they did stimulate increases i...
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Papers by Edgar Wingender