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Binding context flank motif transcription factor

Christian Larney, Timothy L Bailey, Peter Koopman
BACKGROUND: Sex determination in mammals requires expression of the Y-linked gene Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the onset of Sry expression can result in XY sex reversal, highlighting the need for accurate gene regulation during sex determination. However, the location of critical regulatory elements remains unknown. Here, we analysed Sry flanking sequences across many species, using newly available genome sequences and computational tools, to better understand Sry's genomic context and to identify conserved regions predictive of functional roles...
October 6, 2015: BMC Developmental Biology
Brijesh Kumar, Mallikarjunachari V N Uppuladinne, Vinod Jani, Uddhavesh Sonavane, Rajendra R Joshi, Sharmila A Bapat
Slug, a five C2H2 zinc finger (ZF) motif transcription factor mediates cell migration in development, adult tissue repair and regeneration, as well as during tumor metastases through epithelial to mesenchymal transition. At the molecular level, this involves interactions with E-box (CACC/GGTG) consensus elements within target gene promoters to achieve transcriptional repression. However, precise elucidation of events involved in this DNA recognition and binding of specific promoters to regulate target genes have not been achieved...
September 2015: Biochimica et Biophysica Acta
Manu Setty, Christina S Leslie
Genome-wide maps of transcription factor (TF) occupancy and regions of open chromatin implicitly contain DNA sequence signals for multiple factors. We present SeqGL, a novel de novo motif discovery algorithm to identify multiple TF sequence signals from ChIP-, DNase-, and ATAC-seq profiles. SeqGL trains a discriminative model using a k-mer feature representation together with group lasso regularization to extract a collection of sequence signals that distinguish peak sequences from flanking regions. Benchmarked on over 100 ChIP-seq experiments, SeqGL outperformed traditional motif discovery tools in discriminative accuracy...
May 2015: PLoS Computational Biology
Victoria V Mironova, Nadezda A Omelyanchuk, Daniil S Wiebe, Victor G Levitsky
Auxin responsive elements (AuxRE) were found in upstream regions of target genes for ARFs (Auxin response factors). While Chip-seq data for most of ARFs are still unavailable, prediction of potential AuxRE is restricted by consensus models that detect too many false positive sites. Using sequence analysis of experimentally proven AuxREs, we revealed both an extended nucleotide context pattern for AuxRE itself and three distinct types of its coupling motifs (Y-patch, AuxRE-like, and ABRE-like), which together with AuxRE may form the composite elements...
2014: BMC Genomics
Brett J Schuchardt, Vikas Bhat, David C Mikles, Caleb B McDonald, Marius Sudol, Amjad Farooq
The ability of WWOX tumor suppressor to physically associate with the intracellular domain (ICD) of ErbB4 receptor tyrosine kinase is believed to play a central role in downregulating the transcriptional function of the latter. Herein, using various biophysical methods, we show that while the WW1 domain of WWOX binds to PPXY motifs located within the ICD of ErbB4 in a physiologically relevant manner, the WW2 domain does not. Importantly, while the WW1 domain absolutely requires the integrity of the PPXY consensus sequence, nonconsensus residues within and flanking this motif do not appear to be critical for binding...
December 23, 2013: Biochemistry
Delphine Menoret, Marc Santolini, Isabelle Fernandes, Rebecca Spokony, Jennifer Zanet, Ignacio Gonzalez, Yvan Latapie, Pierre Ferrer, Hervé Rouault, Kevin P White, Philippe Besse, Vincent Hakim, Stein Aerts, Francois Payre, Serge Plaza
BACKGROUND: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes...
2013: Genome Biology
Raluca Gordân, Ning Shen, Iris Dror, Tianyin Zhou, John Horton, Remo Rohs, Martha L Bulyk
DNA sequence is a major determinant of the binding specificity of transcription factors (TFs) for their genomic targets. However, eukaryotic cells often express, at the same time, TFs with highly similar DNA binding motifs but distinct in vivo targets. Currently, it is not well understood how TFs with seemingly identical DNA motifs achieve unique specificities in vivo. Here, we used custom protein-binding microarrays to analyze TF specificity for putative binding sites in their genomic sequence context. Using yeast TFs Cbf1 and Tye7 as our case studies, we found that binding sites of these bHLH TFs (i...
April 25, 2013: Cell Reports
Tihomir Miralem, Nicole Lerner-Marmarosh, Peter E M Gibbs, Cicerone Tudor, Fred K Hagen, Mahin D Maines
PKCδ, a Ser/Thr kinase, promotes cell growth, tumorigenesis, and apoptosis. Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase, inhibits apoptosis by reducing biliverdin-IX to antioxidant bilirubin. The enzymes are activated by similar stimuli. Reportedly, hBVR is a kinase-independent activator of PKCδ and is transactivated by the PKC (Gibbs, P. E., Miralem, T., Lerner-Marmarosh, N., Tudor, C., and Maines, M. D. (2012) J. Biol. Chem. 287, 1066-1079). Presently, we examined interactions between the two proteins in the context of regulation of their activities and defining targets of hBVR phosphorylation by PKCδ...
July 13, 2012: Journal of Biological Chemistry
Ran Chachick, Amos Tanay
Nucleotide substitution is a major evolutionary driving force that can incrementally and stochastically give rise to broad divergence patterns among species. The substitution process at each genomic position is frequently modeled independently of the other positions, although complex interactions between nearby bases are known to significantly affect mutation rates. Here, we study the evolution of 12 fly genomes using new algorithms for accurate inference of parameter-rich substitution models. By comparing models between lineages, we reveal the evolutionary histories of substitution rates at different flanking nucleotide contexts...
July 2012: Molecular Biology and Evolution
N A Datson, J A E Polman, R T de Jonge, P T M van Boheemen, E M T van Maanen, J Welten, B S McEwen, H C Meiland, O C Meijer
The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus...
October 2011: Endocrinology
Eric Escobar-Cabrera, Mark Okon, Desmond K W Lau, Christopher F Dart, Alexandre M J J Bonvin, Lawrence P McIntosh
DAXX is a scaffold protein with diverse roles that often depend upon binding SUMO via its N- and/or C-terminal SUMO-interacting motifs (SIM-N and SIM-C). Using NMR spectroscopy, we characterized the in vitro binding properties of peptide models of SIM-N and SIM-C to SUMO-1 and SUMO-2. In each case, binding was mediated by hydrophobic and electrostatic interactions and weakened with increasing ionic strength. Neither isolated SIM showed any significant paralog specificity, and the measured μM range K(D) values of SIM-N toward both SUMO-1 and SUMO-2 were ∼4-fold lower than those of SIM-C...
June 3, 2011: Journal of Biological Chemistry
Francis Bergeron, Edward T Bagu, Jacques J Tremblay
Platelet-derived growth factor (PDGF) A is secreted by Sertoli cells and acts on Leydig precursor cells, which express the receptor PDGFRA, triggering their differentiation into steroidogenically active Leydig cells. There is, however, no information regarding the molecular mechanisms that govern Pdgfra expression in Leydig cells. In this study, we isolated and characterized a 2.2 kb fragment of the rat Pdgfra 5'-flanking sequence in the TM3 Leydig cell line, which endogenously expresses Pdgfra. A series of 5' progressive deletions of the Pdgfra promoter was generated and transfected in TM3 cells...
April 2011: Journal of Molecular Endocrinology
Caroline Sirichandra, Marlène Davanture, Benjamin E Turk, Michel Zivy, Benoît Valot, Jeffrey Leung, Sylvain Merlot
BACKGROUND: Genetic evidence in Arabidopsis thaliana indicates that members of the Snf1-Related Kinases 2 family (SnRK2) are essential in mediating various stress-adaptive responses. Recent reports have indeed shown that one particular member, Open Stomata (OST)1, whose kinase activity is stimulated by the stress hormone abscisic acid (ABA), is a direct target of negative regulation by the core ABA co-receptor complex composed of PYR/PYL/RCAR and clade A Protein Phosphatase 2C (PP2C) proteins...
November 10, 2010: PloS One
Sateesh Kagale, Kevin Rozwadowski
The Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif is a small yet distinct regulatory motif that is conserved in many plant transcriptional regulator (TR) proteins associated with diverse biological functions. We have previously established a list of high-confidence Arabidopsis EAR repressors, the EAR repressome, comprising 219 TRs belonging to 21 different TR families. This class of proteins and the sequence context of the EAR motif exhibited a high degree of conservation across evolutionarily diverse plant species...
June 2010: Plant Signaling & Behavior
Kirsty Flower, Elizabeth Hellen, Melanie J Newport, Susan Jones, Alison J Sinclair
BACKGROUND: Epstein Barr virus (EBV) infects the majority of the human population, causing fatal diseases in a small proportion in conjunction with environmental factors. Following primary infection, EBV remains latent in the memory B cell population for life. Recurrent reactivation of the virus occurs, probably due to activation of the memory B-lymphocytes, resulting in viral replication and re-infection of B-lymphocytes. Methylation of the viral DNA at CpG motifs leads to silencing of viral gene expression during latency...
February 26, 2010: PloS One
Hans Binder, Henry Wirth, Jörg Galle
Our study addresses modes of genomic regulation and their characterization using the distribution of expression values. A simple model of transcriptional regulation is introduced to characterize the response of the global expression pattern to the changing properties of basal regulatory building blocks. Random genomes are generated which express and bind transcription factors according to the appearance of short motifs of coding and binding sequences. Regulation of transcriptional activity is described using a thermodynamic model...
September 1, 2010: Journal of Biotechnology
Linda M Persson, Angus C Wilson
For Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8 [HHV8]), the switch from latency to active lytic replication requires RTA, the product of open reading frame 50 (ORF50). RTA activates transcription from nearly 40 early and delayed-early viral promoters, mainly through interactions with cellular DNA binding proteins, such as CSL/RBP-Jkappa, Oct-1, C/EBPalpha, and c-Jun. Reliance on cellular coregulators may allow KSHV to adjust its lytic program to suit different cellular contexts or interpret signals from the outside...
February 2010: Journal of Virology
Jennifer L Kabat, Sergio Barberan-Soler, Alan M Zahler
Alternative splicing is regulated by cis sequences in the pre-mRNA that serve as binding sites for trans-acting alternative splicing factors. In a previous study, we used bioinformatics and molecular biology to identify and confirm that the intronic hexamer sequence UCUAUC is a nematode alternative splicing regulatory element. In this study, we used RNA affinity chromatography to identify trans factors that bind to this sequence. HRP-2, the Caenorhabditis elegans homolog of human heterogeneous nuclear ribonucleoproteins Q and R, binds to UCUAUC in the context of unc-52 intronic regulatory sequences as well as to RNAs containing tandem repeats of this sequence...
October 16, 2009: Journal of Biological Chemistry
Ganit Yarden, Rofa Elfakess, Kfir Gazit, Rivka Dikstein
The proximal promoter consists of binding sites for transcription regulators and a core promoter. We identified an overrepresented motif in the proximal promoter of human genes with an Initiator (INR) positional bias. The core of the motif fits the INR consensus but its sequence is more strict and flanked by additional conserved sequences. This strict INR (sINR) is enriched in TATA-less genes that belong to specific functional categories. Analysis of the sINR-containing DHX9 and ATP5F1 genes showed that the entire sINR sequence, including the strict core and the conserved flanking sequences, is important for transcription...
July 2009: Nucleic Acids Research
Jay R Hesselberth, Xiaoyu Chen, Zhihong Zhang, Peter J Sabo, Richard Sandstrom, Alex P Reynolds, Robert E Thurman, Shane Neph, Michael S Kuehn, William S Noble, Stanley Fields, John A Stamatoyannopoulos
The orchestrated binding of transcriptional activators and repressors to specific DNA sequences in the context of chromatin defines the regulatory program of eukaryotic genomes. We developed a digital approach to assay regulatory protein occupancy on genomic DNA in vivo by dense mapping of individual DNase I cleavages from intact nuclei using massively parallel DNA sequencing. Analysis of >23 million cleavages across the Saccharomyces cerevisiae genome revealed thousands of protected regulatory protein footprints, enabling de novo derivation of factor binding motifs and the identification of hundreds of new binding sites for major regulators...
April 2009: Nature Methods
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