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Synthetic transcriptional factor

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https://www.readbyqxmd.com/read/28637236/the-ribosome-assembly-gene-network-is-controlled-by-the-feedback-regulation-of-transcription-elongation
#1
Fernando Gómez-Herreros, Thanasis Margaritis, Olga Rodríguez-Galán, Vicent Pelechano, Victoria Begley, Gonzalo Millán-Zambrano, Macarena Morillo-Huesca, Mari Cruz Muñoz-Centeno, José E Pérez-Ortín, Jesús de la Cruz, Frank C P Holstege, Sebastián Chávez
Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis...
June 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28630007/rna-localization-making-its-way-to-the-center-stage
#2
REVIEW
Ashley Chin, Eric Lécuyer
Cells are highly organized entities that rely on intricate addressing mechanisms to sort their constituent molecules to precise subcellular locations. These processes are crucial for cells to maintain their proper organization and carry out specialized functions in the body, while genetic perturbations that clog up these addressing systems can contribute to disease aetiology. The trafficking of RNA molecules represents an important layer in the control of cellular organization, a process that is both highly prevalent and for which features of the regulatory machineries have been deeply conserved evolutionarily...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624538/analysis-of-mrna-deadenylation-by-multi-protein-complexes
#3
Michael W Webster, James A W Stowell, Terence T L Tang, Lori A Passmore
Poly(A) tails are found at the 3' end of almost every eukaryotic mRNA and are important for the stability of mRNAs and their translation into proteins. Thus, removal of the poly(A) tail, a process called deadenylation, is critical for regulation of gene expression. Most deadenylation enzymes are components of large multi-protein complexes. Here, we describe an in vitro deadenylation assay developed to study the exonucleolytic activities of the multi-protein Ccr4-Not and Pan2-Pan3 complexes. We discuss how this assay can be used with short synthetic RNAs, as well as longer RNA substrates generated using in vitro transcription...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28624210/low-dose-gene-therapy-for-murine-pku-using-episomal-naked-dna-vectors-expressing-pah-from-its-endogenous-liver-promoter
#4
Hiu Man Grisch-Chan, Andrea Schlegel, Tanja Scherer, Gabriella Allegri, Raphael Heidelberger, Panagiota Tsikrika, Marco Schmeer, Martin Schleef, Cary O Harding, Johannes Häberle, Beat Thöny
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623587/generation-of-dtales-and-libraries-of-synthetic-tale-activated-promoters-for-engineering-of-gene-regulatory-networks-in-plants
#5
Tom Schreiber, Alain Tissier
Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28621681/overexpression-of-emt-inducing-transcription-factors-as-a-potential-poor-prognostic-factor-for-hepatocellular-carcinoma-in-asian-populations-a-meta-analysis
#6
Tao Wan, Tianwei Zhang, Xiaoying Si, Yanming Zhou
BACKGROUND AND OBJECTIVES: The clinical relevance of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) progression has been highlighted during the last decade. The zinc finger E-box binding homeobox (ZEB) family, the zinc-finger transcriptional repressor (SNAI) family, and the basic helix-loop-helix transcription factor (Twist) family, known as the prominent EMT-inducing transcription factors (EMT-TFs), played a crucial role in the process of EMT. Here, this meta-analysis aimed to evaluate the prognostic value of EMT-TFs high expression in patients with HCC after hepatectomy...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621262/a-peptide-antagonist-of-prep1-p160-interaction-improves-ceramide-induced-insulin-resistance-in-skeletal-muscle-cells
#7
Ilaria Cimmino, Virginia Lorenzo, Francesca Fiory, Nunzianna Doti, Serena Ricci, Serena Cabaro, Antonietta Liotti, Luigi Vitagliano, Michele Longo, Claudia Miele, Pietro Formisano, Francesco Beguinot, Menotti Ruvo, Francesco Oriente
Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake.In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617824/regulation-of-type-1-iodothyronine-deiodinase-by-lxr%C3%AE
#8
Yoriko Sakane, Naotetsu Kanamoto, Ichiro Yamauchi, Tetsuya Tagami, Yusuke Morita, Masako Miura, Masakatsu Sone, Akihiro Yasoda, Takeshi Kimura, Kazuwa Nakao, Nobuya Inagaki
The iodothyronine deiodinases are selenoenzymes that regulate the activity of thyroid hormone via specific inner- or outer-ring deiodination. In humans, type 1 deiodinase (D1) is highly expressed in the liver, but the mechanism by which its gene expression is regulated remains to be elucidated. Liver X receptor α (LXRα), a transcription factor of the nuclear receptor superfamily, is highly expressed in the liver, where it functions as a sensor for excess intracellular oxysterols. LXRα interacts with other nuclear receptors on promoters of genes that contain a binding core sequence for nuclear receptors...
2017: PloS One
https://www.readbyqxmd.com/read/28614654/creation-of-a-synthetic-ligand-for-mitochondrial-dna-sequence-recognition-and-promoter-specific-transcription-suppression
#9
Takuya Hidaka, Ganesh N Pandian, Junichi Taniguchi, Tomohiro Nobeyama, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Synthetic ligands capable of recognizing the specific DNA sequences inside human mitochondria and modulating gene transcription is of increasing demand because of the surge in evidence linking mitochondrial genome and diseases. Herein, we created a new type of mitochondria-specific synthetic ligand, termed MITO-PIPs by conjugating a mitochondria-penetrating peptide with pyrrole-imidazole polyamides (PIPs). The designed MITO-PIPs showed specific localization inside mitochondria in HeLa cells and recognized the target DNA in a sequence-specific manner...
June 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28610919/neural-differentiation-of-human-embryonic-stem-cells-induced-by-the-transgene-mediated-overexpression-of-single-transcription-factors
#10
Misako Matsushita, Yuhki Nakatake, Itaru Arai, Keiji Ibata, Kazuhisa Kohda, Sravan K Goparaju, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B H Ko, Takanori Kanai, Michisuke Yuzaki, Minoru S H Ko
Pluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28607381/wsmd-weakly-supervised-motif-discovery-in-transcription-factor-chip-seq-data
#11
Hongbo Zhang, Lin Zhu, De-Shuang Huang
Although discriminative motif discovery (DMD) methods are promising for eliciting motifs from high-throughput experimental data, due to consideration of computational expense, most of existing DMD methods have to choose approximate schemes that greatly restrict the search space, leading to significant loss of predictive accuracy. In this paper, we propose Weakly-Supervised Motif Discovery (WSMD) to discover motifs from ChIP-seq datasets. In contrast to the learning strategies adopted by previous DMD methods, WSMD allows a "global" optimization scheme of the motif parameters in continuous space, thereby reducing the information loss of model representation and improving the quality of resultant motifs...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601309/the-aryl-hydrocarbon-receptor-as-an-antitumor-target-of-synthetic-curcuminoids-in-colorectal-cancer
#12
Bryant W Megna, Patrick R Carney, Mitchell G Depke, Manabu Nukaya, James McNally, Lesley Larsen, Rhonda J Rosengren, Gregory D Kennedy
BACKGROUND: Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our laboratory has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin's role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28596760/in-depth-profiling-of-mvfr-regulated-small-molecules-in-pseudomonas-aeruginosa-after-quorum-sensing-inhibitor-treatment
#13
Giuseppe Allegretta, Christine K Maurer, Jens Eberhard, Damien Maura, Rolf W Hartmann, Laurence Rahme, Martin Empting
Pseudomonas aeruginosa is a Gram-negative bacterium, which causes opportunistic infections in immuno-compromised individuals. Due to its multiple resistances toward antibiotics, the development of new drugs is required. Interfering with Quorum Sensing (QS), a cell-to-cell communication system, has shown to be highly efficient in reducing P. aeruginosa pathogenicity. One of its QS systems employs Pseudomonas Quinolone Signal (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signal molecules. Both activate the transcriptional regulator MvfR (Multiple Virulence Factor Regulator), also called PqsR, driving the production of QS molecules as well as toxins and biofilm formation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28594167/toward-an-expanded-genome-structural-and-computational-characterization-of-an-artificially-expanded-genetic-information-system
#14
Nigel G J Richards, Millie M Georgiadis
Although the fundamental properties of DNA as first proposed by Watson and Crick in 1953 provided a basic understanding of how duplex DNA was organized and might be replicated, it was not until the first crystal structures of DNA (Z-DNA in 1979, B-DNA in 1980, and A-DNA in 1982) that the true complexity of the molecule began to be appreciated. Many crystal structures of oligonucleotides have since shed light on the helical forms that "Watson-Crick" DNA can adopt, their associated groove widths, and the properties of the nucleobase pairs and their interactions in all three helical forms...
June 8, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28592994/effects-of-global-transcription-factor-ntca-on-photosynthetic-production-of-ethylene-in-recombinant-synechocystis-sp-pcc-6803
#15
Huilin Mo, Xiaoman Xie, Tao Zhu, Xuefeng Lu
BACKGROUND: Cyanobacteria are considered potential photosynthetic microbial cell factories for biofuel and biochemical production. Ethylene, one of the most important organic chemicals, has been successfully synthesized in cyanobacteria by introducing an exogenous ethylene-forming enzyme (Efe). However, it remains challenging to significantly improve the biosynthetic efficiency of cyanobacterial ethylene. Genetic modification of transcription factors is a powerful strategy for reprogramming cellular metabolism toward target products...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28592498/genetic-dissection-of-nutrition-induced-plasticity-in-insulin-insulin-like-growth-factor-signaling-and-median-life-span-in-a-drosophila-multiparent-population
#16
Patrick D Stanley, Enoch Ng'oma, Siri O'Day, Elizabeth G King
The nutritional environments that organisms experience are inherently variable, requiring tight coordination of how resources are allocated to different functions relative to the total amount of resources available. A growing body of evidence supports the hypothesis that key endocrine pathways play a fundamental role in this coordination. In particular, the insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways have been implicated in nutrition-dependent changes in metabolism and nutrient allocation...
June 2017: Genetics
https://www.readbyqxmd.com/read/28590087/structural-states-of-ror%C3%AE-t-x-ray-elucidation-of-molecular-mechanisms-and-binding-interactions-for-natural-and-synthetic-compounds
#17
Joerg Kallen, Aude Izaac, Celine Be, Luca Arista, David Orain, Klemens Kaupmann, Christine Guntermann, Klemens Hoegenauer, Samuel Hintermann
RORγt is a key transcription factor for the production of pro-inflammatory Th17 cytokines which are implicated in the pathogenesis of autoimmune diseases. We have recently reported a new series of inverse agonists based on an imidazopyridine core with good physicochemical properties and excellent selectivity. Here we report eight new X-ray structures for different classes of natural and synthetic compounds including examples selected from the patent literature. An analysis of their respective binding modes reveals insights into the molecular mechanisms leading to agonism, antagonism or inverse agonism...
June 7, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28589121/pancreatic-beta-cell-identity-in-humans-and-the-role-of-type-2-diabetes
#18
REVIEW
Piero Marchetti, Marco Bugliani, Vincenzo De Tata, Mara Suleiman, Lorella Marselli
Pancreatic beta cells uniquely synthetize, store, and release insulin. Specific molecular, functional as well as ultrastructural traits characterize their insulin secretion properties and survival phentoype. In this review we focus on human islet/beta cells, and describe the changes that occur in type 2 diabetes and could play roles in the disease as well as represent possible targets for therapeutical interventions. These include transcription factors, molecules involved in glucose metabolism and insulin granule handling...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28589100/microrna-21-limits-uptake-of-listeria-monocytogenes-by-macrophages-to-reduce-the-intracellular-niche-and-control-infection
#19
Daniel G W Johnston, Jay Kearney, Zbigniew Zasłona, Michelle A Williams, Luke A J O'Neill, Sinéad C Corr
MiRNAs are important post-transcriptional regulators of gene expression. MiRNA expression is a crucial part of host responses to bacterial infection, however there is limited knowledge of their impact on the outcome of infections. We investigated the influence of miR-21 on macrophage responses during infection with Listeria monocytogenes, which establishes an intracellular niche within macrophages. MiR-21 is induced following infection of bone marrow-derived macrophages (BMDMs) with Listeria. MiR-21(-/-) macrophages display an increased bacterial burden with Listeria at 30 min and 2 h post-infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28588129/complete-biosynthesis-of-anthocyanins-using-e-coli-polycultures
#20
J Andrew Jones, Victoria R Vernacchio, Shannon M Collins, Abhijit N Shirke, Yu Xiu, Jacob A Englaender, Brady F Cress, Catherine C McCutcheon, Robert J Linhardt, Richard A Gross, Mattheos A G Koffas
Fermentation-based chemical production strategies provide a feasible route for the rapid, safe, and sustainable production of a wide variety of important chemical products, ranging from fuels to pharmaceuticals. These strategies have yet to find wide industrial utilization due to their inability to economically compete with traditional extraction and chemical production methods. Here, we engineer for the first time the complex microbial biosynthesis of an anthocyanin plant natural product, starting from sugar...
June 6, 2017: MBio
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