ConTra v3 : a tool to identify transcription factor binding sites across species, update 2017

Transcription factors are important gene regulators with distinctive roles in development, cell signaling and cell cycling, and they have been associated with many diseases. The ConTra v3 web server allows easy visualization and exploration of predicted transcription factor binding sites (TFBSs) in any genomic region surrounding coding or non-coding genes. In this updated version, with a completely re-implemented user interface using latest web technologies, users can choose from nine reference organisms ranging from human to yeast. ConTra v3 can analyze promoter regions, 5'-UTRs, 3'-UTRs and introns or any other genomic region of interest. Thousands of position weight matrices are available to choose from for detecting specific binding sites. Besides this visualization option, additional new exploration functionality is added to the tool that will automatically detect TFBSs having at the same time the highest regulatory potential, the highest conservation scores of the genomic regions covered by the predicted TFBSs and strongest co-localizations with genomic regions exhibiting regulatory activity. The ConTra v3 web server is freely available at http://bioit2.irc.ugent.be/contra/v3

Armc8 is a evolutionarily conserved armadillo protein involved in cell-cell adhesion complexes through multiple molecular interactions

Armadillo-repeat-containing protein 8 (Armc8) belongs to the family of armadillo-repeat containing proteins, which have been found to be involved in diverse cellular functions including cell-cell contacts and intracellular signaling. By comparative analyses of armadillo repeat protein structures and genomes from various premetazoan and metazoan species, we identified orthologs of human Armc8 and analyzed in detail the evolutionary relationship of Armc8 genes and their encoded proteins. Armc8 is a highly ancestral armadillo protein although not present in yeast. Consequently, Armc8 is not the human ortholog of yeast Gid5/Vid28. Further, we performed a candidate approach to characterize new protein interactors of Armc8. Interactions between Armc8 and specific delta-catenins (plakophilins-1, -2, -3 and p0071) were observed by the yeast two-hybrid approach and confirmed by co-immunoprecipitation and co-localization. We also showed that Armc8 interacts specifically with alpha E-catenin but neither with alpha N-catenin nor with alpha T-catenin. Degradation of alpha E-catenin has been reported to be important in cancer and to be regulated by Armc8. A similar process may occur with respect to plakophilins in desmosomes. Deregulation of desmosomal proteins has been considered to contribute to tumorigenesis

Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein

The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.Fil: Linero, Florencia Natalia. Flanders Interuniversity Institute For Biotechnology; Bélgica. University of Ghent; BélgicaFil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Christopoulou, Ioanna. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Hulpiau, Paco. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; BélgicaFil: Scolaro, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Saelens, Xavier. University of Ghent; Bélgica. Flanders Interuniversity Institute For Biotechnology; Bélgic

Text-mining assisted regulatory annotation

Text-mining technologies can be integrated with genome annotation systems, increasing the availability of annotated cis-regulatory data

Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions

The CARD-coiled coil (CC)/Bcl10/MALT1-like paracaspase (CBM) signaling complexes composed of a CARD-CC family member (CARD-9, -10, -11, or -14), Bcl10, and the type 1 paracaspase MALT1 (PCASP1) play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians). Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects) lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD-CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD-CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein-protein interactions, NF-kappa B signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-kappa B-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1

ConTra v2: a tool to identify transcription factor binding sites across species, update 2011

Transcription factors are important gene regulators with distinctive roles in development, cell signaling and cell cycling, and they have been associated with many diseases. The ConTra v2 web server allows easy visualization and exploration of predicted transcription factor binding sites in any genomic region surrounding coding or non-coding genes. In this new version, users can choose from nine reference organisms ranging from human to yeast. ConTra v2 can analyze promoter regions, 5′-UTRs, 3′-UTRs and introns or any other genomic region of interest. Hundreds of position weight matrices are available to choose from, but the user can also upload any other matrices for detecting specific binding sites. A typical analysis is run in four simple steps of choosing the gene, the transcript, the region of interest and then selecting one or more transcription factor binding sites. The ConTra v2 web server is freely available at http://bioit.dmbr.ugent.be/contrav2/index.php

ConTra: a promoter alignment analysis tool for identification of transcription factor binding sites across species

Transcription factors (TFs) are key components in signaling pathways, and the presence of their binding sites in the promoter regions of DNA is essential for their regulation of the expression of the corresponding genes. Orthologous promoter sequences are commonly used to increase the specificity with which potentially functional transcription factor binding sites (TFBSs) are recognized and to detect possibly important similarities or differences between the different species. The ConTra (conserved TFBSs) web server provides the biologist at the bench with a user-friendly tool to interactively visualize TFBSs predicted using either TransFac (1) or JASPAR (2) position weight matrix libraries, on a promoter alignment of choice. The visualization can be preceded by a simple scoring analysis to explore which TFs are the most likely to bind to the promoter of interest. The ConTra web server is available at http://bioit.dmbr.ugent.be/ConTra/index.php

Formin is associated with left-right asymmetry in the pond snail and the frog

While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signalling of Nodal, downstream of symmetry-breaking, may be an ancestral feature of the Bilateria. Here we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry-breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or over-expression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models, we discovered asymmetric gene expression in 2 and 4 cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro, together these results are consistent with the view that animals with diverse bodyplans may derive their asymmetries from the same intracellular chiral elements