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Transcriptional elongation

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https://www.readbyqxmd.com/read/28930680/systematic-kinase-inhibitor-profiling-identifies-cdk9-as-a-synthetic-lethal-target-in-nut-midline-carcinoma
#1
Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz, Peter Habenberger, Zhizhou Fang, Sandra Ortiz-Cuaran, Frauke Leenders, Jan Eickhoff, Uwe Koch, Matthäus Getlik, Martin Termathe, Muhammad Sallouh, Zoltán Greff, Zoltán Varga, Hyatt Balke-Want, Christopher A French, Martin Peifer, H Christian Reinhardt, László Örfi, György Kéri, Sascha Ansén, Lukas C Heukamp, Reinhard Büttner, Daniel Rauh, Bert M Klebl, Roman K Thomas, Martin L Sos
Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930676/localized-phosphorylation-of-a-kinesin-1-adaptor-by-a-capsid-associated-kinase-regulates-hiv-1-motility-and-uncoating
#2
Viacheslav Malikov, Mojgan H Naghavi
Although microtubule motors mediate intracellular virus transport, the underlying interactions and control mechanisms remain poorly defined. This is particularly true for HIV-1 cores, which undergo complex, interconnected processes of cytosolic transport, reverse transcription, and uncoating of the capsid shell. Although kinesins have been implicated in regulating these events, curiously, there are no direct kinesin-core interactions. We recently showed that the capsid-associated kinesin-1 adaptor protein, fasciculation and elongation protein zeta-1 (FEZ1), regulates HIV-1 trafficking...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28923978/mcam-contributes-to-the-establishment-of-cell-autonomous-polarity-in-myogenic-and-chondrogenic-differentiation
#3
Artal Moreno-Fortuny, Laricia Bragg, Giulio Cossu, Urmas Roostalu
Cell polarity has a fundamental role in shaping the morphology of cells and growing tissues. Polarity is commonly thought to be established in response to extracellular signals. Here we used a minimal in vitro assay that enabled us to monitor the determination of cell polarity in myogenic and chondrogenic differentiation in the absence of external signalling gradients. We demonstrate that the initiation of cell polarity is regulated by melanoma cell adhesion molecule (MCAM). We found highly polarized localization of MCAM, Moesin (MSN), Scribble (SCRIB) and Van-Gogh-like 2 (VANGL2) at the distal end of elongating myotubes...
September 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28919888/the-sporothrix-schenckii-gene-encoding-for-the-ribosomal-protein-l6-has-constitutive-and-stable-expression-and-works-as-an-endogenous-control-in-gene-expression-analysis
#4
Elías Trujillo-Esquivel, José A Martínez-Álvarez, Diana M Clavijo-Giraldo, Nahúm V Hernández, Alberto Flores-Martínez, Patricia Ponce-Noyola, Héctor M Mora-Montes
Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28916594/della-gaf1-complex-is-a-main-component-in-gibberellin-feedback-regulation-of-ga20ox2-in-arabidopsis
#5
Jutarou Fukazawa, Masahiko Mori, Satoshi Watanabe, Chika Miyamoto, Takeshi Ito, Yohsuke Takahashi
Gibberellins (GAs) are phytohormones that regulate many aspects of plant growth and development, including germination, elongation, flowering, and floral development. Negative feedback regulation contributes to homeostasis of the GA level. DELLAs are negative regulators of GA signaling and are rapidly degraded in the presence of GAs. DELLAs regulate many target genes, including AtGA20ox2, encoding the GA-biosynthetic enzyme GA 20-oxidase. As DELLAs do not have an apparent DNA-binding motif, transcription factors that act in association with DELLA are necessary for regulating the target genes...
September 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28914981/fna-cytology-of-solitary-fibrous-tumors-and-the-diagnostic-value-of-stat6-immunocytochemistry
#6
Edneia Tani, Johan Wejde, Kristina Åström, Inga-Lill Wingmo, Olle Larsson, Felix Haglund
BACKGROUND: Solitary fibrous tumors (SFTs) are rare mesenchymal tumors commonly located in the pleura, soft tissues, or meninges and are characterized by the NGFI-A-binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion gene. Recent studies have indicated that nuclear STAT6 immunohistochemistry is a specific marker for SFTs. METHODS: The authors reviewed fine-needle aspiration (FNA) specimens from extracranial SFTs diagnosed at their institution between 1993 and 2017...
September 15, 2017: Cancer
https://www.readbyqxmd.com/read/28912063/differential-expression-by-chromatin-modifications-of-alcohol-dehydrogenase-1-of-chorispora-bungeana-in-cold-stress
#7
Lijun Liu, Yuan Song, Jun Xu, Dongming Li, Gaopeng Li, Lizhe An
Epigenetic modifications regulate plant genes to cope with a variety of environmental stresses. Chorispora bungeana is an alpine subnival plant with strong tolerance to multiple abiotic stresses, especially cold stress. In this study, we characterized the alcohol dehydrogenase 1 gene from Chorispora bungeana, CbADH1, that is up-regulated in cold conditions. Overexpression of CbADH1 in Arabidopsis thaliana improved cold tolerance, as indicated by a decreased lethal temperature (LT50). Chromatin immunoprecipitation assays showed that histone H3 is removed from the promoter region and the middle-coding region of the gene...
September 11, 2017: Gene
https://www.readbyqxmd.com/read/28904013/integrative-analysis-of-rna-polymerase-ii-and-transcriptional-dynamics-upon-myc-activation
#8
Stefano de Pretis, Theresia R Kress, Marco J Morelli, Arianna Sabò, Chiara Locarno, Alessandro Verrecchia, Mirko Doni, Stefano Campaner, Bruno Amati, Mattia Pelizzola
Overexpression of the MYC transcription factor causes its widespread interaction with regulatory elements in the genome but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following MYC activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing, and mathematical modeling...
September 13, 2017: Genome Research
https://www.readbyqxmd.com/read/28902388/transcriptional-repression-in-macrophages-basic-mechanisms-and-alterations-in-metabolic-inflammatory-diseases
#9
REVIEW
Eckardt Treuter, Rongrong Fan, Zhiqiang Huang, Tomas Jakobsson, Nicolas Venteclef
Macrophage differentiation and signal responses are coordinated by closely linked transcriptional and epigenomic mechanisms that trigger gene expression. In contrast to well-characterized transcriptional activation pathways in response to diverse metabolic and inflammatory signals, we just begin appreciating that transcriptional repression is equally important. Here we will highlight macrophage pathways that are controlled by multifaceted repression events, along with a discussion of underlying regulatory mechanisms and components...
September 13, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28893556/the-ilk-mmp9-mrtf-axis-is-crucial-for-endmt-differentiation-of-endothelial-cells-in-a-tumor-microenvironment
#10
Wojciech M Ciszewski, Katarzyna Sobierajska, Marta E Wawro, Wanda Klopocka, Natasza Chefczyńska, Angelika Muzyczuk, Kamil Siekacz, Agata Wujkowska, Jolanta Niewiarowska
Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). EndMT is mainly promoted by the Transforming Growth Factor-β (TGF-β) family secreted by tumor cells, though the role of particular members in EndMT regulation remains poorly understood...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28893534/solution-structure-of-the-n-terminal-domain-of-mediator-subunit-med26-and-molecular-characterization-of-its-interaction-with-eaf1-and-taf7
#11
Zoé Lens, François-Xavier Cantrelle, Riccardo Peruzzini, Xavier Hanoulle, Frédérique Dewitte, Elisabeth Ferreira, Jean-Luc Baert, Didier Monté, Marc Aumercier, Vincent Villeret, Alexis Verger, Isabelle Landrieu
MED26 is a subunit of Mediator, a large complex central to the regulation of gene transcription by RNA Polymerase II (RNA Pol II). MED26 plays a role in the switch between the initiation and elongation phases of RNA Pol II-mediated transcription process. Regulation of these steps requires successive binding of MED26 N-Terminal domain (NTD) to TBP-associated factor 7 (TAF7) and EAF1 (Eleven-nineteen lysine-rich in leukemia-Associated Factor 1). In order to investigate the mechanism of regulation by MED26, MED26-NTD structure was solved by nuclear magnetic resonance spectroscopy (NMR), revealing a 4-helix bundle...
September 9, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28893424/quantifying-the-influence-of-5-rna-modifications-on-rna-polymerase-i-activity
#12
Francis D Appling, Aaron L Lucius, David A Schneider
For ensemble and single-molecule analyses of transcription, the use of synthetic transcription elongation complexes has been a versatile and powerful tool. However, structural analyses demonstrate that short RNA substrates, often employed in these assays, would occupy space within the RNA polymerase. Most commercial RNA oligonucleotides do not carry a 5'-triphosphate as would be present on a natural, de novo synthesized RNA. To examine the effects of 5'-moities on transcription kinetics, we measured nucleotide addition and 3'-dinucleotide cleavage by eukaryotic RNA polymerase I using 5'-hydroxyl and 5'-triphosphate RNA substrates...
September 1, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28892040/structure-of-a-transcribing-rna-polymerase-ii-dsif-complex-reveals-a-multidentate-dna-rna-clamp
#13
Carrie Bernecky, Jürgen M Plitzko, Patrick Cramer
During transcription, RNA polymerase II (Pol II) associates with the conserved elongation factor DSIF. DSIF renders the elongation complex stable and functions during Pol II pausing and RNA processing. We combined cryo-EM and X-ray crystallography to determine the structure of the mammalian Pol II-DSIF elongation complex at a nominal resolution of 3.4 Å. Human DSIF has a modular structure with two domains forming a DNA clamp, two domains forming an RNA clamp, and one domain buttressing the RNA clamp. The clamps maintain the transcription bubble, position upstream DNA, and retain the RNA transcript in the exit tunnel...
September 11, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28886694/comparative-transcriptome-analysis-of-cotton-fiber-development-of-upland-cotton-gossypium-hirsutum-and-chromosome-segment-substitution-lines-from-g-hirsutum-%C3%A3-g-barbadense
#14
Peng-Tao Li, Mi Wang, Quan-Wei Lu, Qun Ge, Md Harun Or Rashid, Ai-Ying Liu, Ju-Wu Gong, Hai-Hong Shang, Wan-Kui Gong, Jun-Wen Li, Wei-Wu Song, Li-Xue Guo, Wei Su, Shao-Qi Li, Xiao-Ping Guo, Yu-Zhen Shi, You-Lu Yuan
BACKGROUND: How to develop new cotton varieties possessing high yield traits of Upland cotton and superior fiber quality traits of Sea Island cotton remains a key task for cotton breeders and researchers. While multiple attempts bring in little significant progresses, the development of Chromosome Segment Substitution Lines (CSSLs) from Gossypium barbadense in G. hirsutum background provided ideal materials for aforementioned breeding purposes in upland cotton improvement. Based on the excellent fiber performance and relatively clear chromosome substitution segments information identified by Simple Sequence Repeat (SSR) markers, two CSSLs, MBI9915 and MBI9749, together with the recurrent parent CCRI36 were chosen to conduct transcriptome sequencing during the development stages of fiber elongation and Secondary Cell Wall (SCW) synthesis (from 10DPA and 28DPA), aiming at revealing the mechanism of fiber development and the potential contribution of chromosome substitution segments from Sea Island cotton to fiber development of Upland cotton...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28886274/the-plant-rna-polymerase-ii-elongation-complex-a-hub-coordinating-transcript-elongation-and-mrna-processing
#15
Marion Grasser, Klaus D Grasser
Characterisation of the Arabidopsis RNA polymerase II (RNAPII) elongation complex revealed an assembly of a conserved set of transcript elongation factors associated with chromatin remodellers, histone modifiers as well as with various pre-mRNA splicing and polyadenylation factors. Therefore, transcribing RNAPII streamlines the processes of mRNA synthesis and processing in plants.
September 8, 2017: Transcription
https://www.readbyqxmd.com/read/28882896/transcriptional-fidelities-of-human-mitochondrial-polrmt-yeast-mitochondrial-rpo41-and-phage-t7-single-subunit-rna-polymerases
#16
Shemaila Sultana, Mihai Solotchi, Aparna Ramachandran, Smita S Patel
Single-subunit RNA polymerases (RNAPs) are present in phage T7 and in mitochondria of all eukaryotes. This RNAP class plays important roles in biotechnology and cellular energy production, but we know little about its fidelity and error rates. Herein, we report the error rates of three single-subunit RNAPs measured from the catalytic efficiencies of correct and all possible incorrect nucleotides. The average error rate of T7 RNAP (2×10-6), yeast mitochondrial Rpo41 (6×10-6), and human mitochondrial POLRMT (2×10-5) indicates high accuracy/fidelity of RNA synthesis resembling those of replicative DNA polymerases...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28881277/functional-identification-of-mdpif1-as-a-phytochrome-interacting-factor-in-apple
#17
Li-Jie Zhou, Ke Mao, Yu Qiao, Han Jiang, Yuan-Yuan Li, Yu-Jin Hao
Light plays a central role in regulating both apple plant yield and fruit quality formation; however, the Phytochrome interacting factors (PIFs), which are the main components of Phytochrome-mediated light signal transduction in apple, have rarely been characterized. Here, we isolated and identified a PIF-like protein(MdPIF1) in apple, which is similar to AtPIF1. MdPIF1 was constitutively expressed at different levels in various apple tissues, and the transcription level of MdPIF1 was significantly induced during seed germination...
August 31, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28878233/a-chalcone-derivative-reactivates-latent-hiv-1-transcription-through-activating-p-tefb-and-promoting-tat-sec-interaction-on-viral-promoter
#18
Jun Wu, Ming-Tao Ao, Rui Shao, Hui-Ru Wang, Diao Yu, Mei-Juan Fang, Xiang Gao, Zhen Wu, Qiang Zhou, Yu-Hua Xue
The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877480/a-defective-mrna-cleavage-and-polyadenylation-complex-facilitates-expansions-of-transcribed-gaa-n-repeats-associated-with-friedreich-s-ataxia
#19
Ryan J McGinty, Franco Puleo, Anna Y Aksenova, Julia A Hisey, Alexander A Shishkin, Erika L Pearson, Eric T Wang, David E Housman, Claire Moore, Sergei M Mirkin
Expansions of microsatellite repeats are responsible for numerous hereditary diseases in humans, including myotonic dystrophy and Friedreich's ataxia. Whereas the length of an expandable repeat is the main factor determining disease inheritance, recent data point to genomic trans modifiers that can impact the likelihood of expansions and disease progression. Detection of these modifiers may lead to understanding and treating repeat expansion diseases. Here, we describe a method for the rapid, genome-wide identification of trans modifiers for repeat expansion in a yeast experimental system...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28865032/regulation-of-skeletal-myoblast-differentiation-by-drebrin
#20
Robert S Krauss
Myoblast differentiation is a complex process. As myoblasts differentiate into myofibers, they acquire a cell type-specific transcriptional program, irreversibly exit the cell cycle, and dramatically change their morphology. The morphological changes include cell elongation, alignment, and fusion into syncytial myofibers. Several lines of evidence suggest that these events may be co-regulated. However, the mechanisms that coordinate major alterations in a cell's transcriptome and its shape are not well understood...
2017: Advances in Experimental Medicine and Biology
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