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Essential genes

Nicoletta Bobola, Samir Merabet
Homeodomain proteins are evolutionary conserved proteins present in the entire eukaryote kingdom. They execute functions that are essential for life, both in developing and adult organisms. Most homeodomain proteins act as transcription factors and bind DNA to control the activity of other genes. In contrast to their similar DNA binding specificity, homeodomain proteins execute highly diverse and context-dependent functions. Several factors, including genome accessibility, DNA shape, combinatorial binding and the ability to interact with many transcriptional partners, diversify the activity of homeodomain proteins and culminate in the activation of highly dynamic, context-specific transcriptional programs...
October 18, 2016: Current Opinion in Genetics & Development
Deepa Khare, Nobukata Mitsuda, Seungchul Lee, Won-Yong Song, Daehee Hwang, Masaru Ohme-Takagi, Enrico Martinoia, Youngsook Lee, Jae-Ung Hwang
Plants reorganize their root architecture to avoid growth into unfavorable regions of the rhizosphere. In a screen based on chimeric repressor gene-silencing technology, we identified the Arabidopsis thaliana GeBP-LIKE 4 (GPL4) transcription factor as an inhibitor of root growth that is induced rapidly in root tips in response to cadmium (Cd). We tested the hypothesis that GPL4 functions in the root avoidance of Cd by analyzing root proliferation in split medium, in which only half of the medium contained toxic concentrations of Cd...
October 21, 2016: New Phytologist
Divya Singh, Ghanshyam Upadhyay, Ananya Sengupta, Mohammed A Biplob, Shaleen Chakyayil, Tiji George, Shireen Saleque
Understanding the production and differentiation of megakaryocytes from progenitors is crucial for realizing the biology and functions of these vital cells. Previous gene ablation studies demonstrated the essential role of the transcriptional repressor Gfi1b (growth factor independence 1b) in the generation of both erythroid and megakaryocytic cells. However, our recent work has demonstrated the down-regulation of this factor during megakaryocytic differentiation. In this study we identify two new gene targets of Gfi1b, the cytoskeletal proteins Kindlin3 and Talin1, and demonstrate the inverse expression and functions of these cytoskeletal targets relative to Gfi1b, during megakaryocytic differentiation...
2016: PloS One
Anna J MacDonald, Stephen D Sarre
Taxon-specific DNA tests are applied to many ecological and management questions, increasingly using environmental DNA (eDNA). eDNA facilitates non-invasive ecological studies, but introduces additional risks of bias and error. For effective application, PCR primers must be developed for each taxon and validated in each system. We outline a nine step framework for the development and validation of taxon-specific primers for eDNA analysis in ecological studies, involving reference database construction, phylogenetic evaluation of the target gene, primer design, primer evaluation in silico, and laboratory evaluation of primer specificity, sensitivity, and utility...
October 21, 2016: Molecular Ecology Resources
Cristina Rodríguez, Tomás Sobrino, Jesús Agulla, Verónica Bobo-Jiménez, María E Ramos-Araque, Juan J Duarte, José C Gómez-Sánchez, Juan P Bolaños, José Castillo, Ángeles Almeida
Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein...
October 21, 2016: Cell Death and Differentiation
Meital Charni, Ronit Aloni-Grinstein, Alina Molchadsky, Varda Rotter
Regeneration and tumorigenesis share common molecular pathways, nevertheless the outcome of regeneration is life, whereas tumorigenesis leads to death. Although the process of regeneration is strictly controlled, malignant transformation is unrestrained. In this review, we discuss the involvement of TP53, the major tumor-suppressor gene, in the regeneration process. We point to the role of p53 as coordinator assuring that regeneration will not shift to carcinogenesis. The fluctuation in p53 activity during the regeneration process permits a tight control...
October 21, 2016: Cell Death and Differentiation
Kristin Bösch, Lamprinos Frantzeskakis, Miroslav Vraneš, Jörg Kämper, Kerstin Schipper, Vera Göhre
Gene deletion plays an important role in the analysis of gene function. One of the most efficient methods to disrupt genes in a targeted manner is the replacement of the entire gene with a selectable marker via homologous recombination. During homologous recombination, exchange of DNA takes place between sequences with high similarity. Therefore, linear genomic sequences flanking a target gene can be used to specifically direct a selectable marker to the desired integration site. Blunt ends of the deletion construct activate the cell's DNA repair systems and thereby promote integration of the construct either via homologous recombination or by non-homologous-end-joining...
September 30, 2016: Journal of Visualized Experiments: JoVE
Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
Inimary T Toby, Mikhail K Levin, Edward A Salinas, Scott Christley, Sanchita Bhattacharya, Felix Breden, Adam Buntzman, Brian Corrie, John Fonner, Namita T Gupta, Uri Hershberg, Nishanth Marthandan, Aaron Rosenfeld, William Rounds, Florian Rubelt, Walter Scarborough, Jamie K Scott, Mohamed Uduman, Jason A Vander Heiden, Richard H Scheuermann, Nancy Monson, Steven H Kleinstein, Lindsay G Cowell
BACKGROUND: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens...
October 6, 2016: BMC Bioinformatics
Ryo Amano, Kenta Takada, Yoichiro Tanaka, Yoshikazu Nakamura, Gota Kawai, Tomoko Kozu, Taiichi Sakamoto
AML1 (RUNX1) protein is an essential transcription factor involved in the development of hematopoietic cells. Several genetic aberrations that disrupt the function of AML1 have been frequently observed in human leukemia. AML1 contains a DNA-binding domain known as the Runt domain (RD), which recognizes the RD-binding double-stranded DNA element of target genes. In this study, we identified high-affinity RNA aptamers that bind to RD by SELEX. The binding assay using surface plasmon resonance indicated that a shortened aptamer retained the ability to bind to RD when 1 M potassium acetate was used...
October 21, 2016: Biochemistry
Daniela Albanesi, Diego de Mendoza
Phospholipids and fatty acids are not only one of the major components of cell membranes but also important metabolic intermediates in bacteria. Since the fatty acid biosynthetic pathway is essential and energetically expensive, organisms have developed a diversity of homeostatic mechanisms to fine-tune the concentration of lipids at particular levels. FapR is the first global regulator of lipid synthesis discovered in bacteria and is largely conserved in Gram-positive organisms including important human pathogens, such as Staphylococcus aureus, Bacillus anthracis, and Listeria monocytogenes...
2016: Frontiers in Molecular Biosciences
Gary K Scott, David Chu, Ravneet Kaur, Julia Malato, Daniel E Rothschild, Katya Frazier, Serenella Eppenberger-Castori, Byron Hann, Ben Ho Park, Christopher C Benz
ERα phosphorylation at hinge site S294 (pS294) was recently shown to be essential for ER-dependent gene transcription and mediated by an unknown cyclin-dependent kinase (CDK). This study was undertaken to identify the exact CDK pathway mediating pS294 formation, and to determine if this phosphorylation event occurs with, and can be targeted to treat, the ligand-independent growth of breast cancers expressing endocrine-refractory ESR1 mutations. Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression...
October 18, 2016: Oncotarget
Marianne Ronovsky, Stefanie Berger, Alice Zambon, Sonali N Reisinger, Orsolya Horvath, Arnold Pollak, Claudia Lindtner, Angelika Berger, Daniela D Pollak
Gestational infection is increasingly being recognized for its involvement as causative mechanism in severe developmental brain abnormalities and its contribution to the pathogenesis of psychopathologies later in life. First observations in the widely accepted maternal immune activation (MIA) model based upon the systemic administration of the viral mimetic Polyinosinic:polycytidylic acid (poly(I:C)) have recently suggested a transmission of behavioral and transcriptional traits across generations. Although maternal care behavior (MCB) is known as essential mediator of the transgenerational effects of environmental challenges on offspring brain function and behavior, the possible propagation of alterations of MCB resulting from MIA to following generations has not yet been examined...
October 17, 2016: Brain, Behavior, and Immunity
Melanie Ott, Débora Marques, Christina Funk, Susanne M Bailer
BACKGROUND: Herpes simplex virus type 1 (HSV1), a member of the alphaherpesvirinae, can cause recurrent facial lesions and encephalitis. Two membrane envelopment processes, one at the inner nuclear membrane and a second at cytoplasmic membranes are crucial for a productive viral infection. Depending on the subfamily, herpesviruses encode more than 11 different transmembrane proteins including members of the tail-anchored protein family. HSV1 encodes three tail-anchored proteins pUL34, pUL56 and pUS9 characterized by a single hydrophobic region positioned at their C-terminal end that needs to be released from the ribosome prior to posttranslational membrane insertion...
October 20, 2016: Virology Journal
Jenna F DuMond, Xue Zhang, Yuichiro Izumi, Kevin Ramkissoon, Guanghui Wang, Marjan Gucek, Xujing Wang, Maurice B Burg, Joan D Ferraris
NFAT5 is a transcription factor originally identified because it is activated by hypertonicity and that activation increases expression of genes that protect against the adverse effects of the hypertonicity. However, its targets also include genes not obviously related to tonicity. The transactivating domain of NFAT5 is contained in its c-terminal region, which is predicted to be unstructured. Unstructured regions are common in transcription factors particularly in transactivating domains where they can bind co-regulatory proteins essential to their function...
October 7, 2016: Physiological Genomics
Sheel Shah, Eric Lubeck, Wen Zhou, Long Cai
Identifying the spatial organization of tissues at cellular resolution from single-cell gene expression profiles is essential to understanding biological systems. Using an in situ 3D multiplexed imaging method, seqFISH, we identify unique transcriptional states by quantifying and clustering up to 249 genes in 16,958 cells to examine whether the hippocampus is organized into transcriptionally distinct subregions. We identified distinct layers in the dentate gyrus corresponding to the granule cell layer and the subgranular zone and, contrary to previous reports, discovered that distinct subregions within the CA1 and CA3 are composed of unique combinations of cells in different transcriptional states...
October 19, 2016: Neuron
Toshiaki Okada, Md Rafiqul Islam, Nargiza A Tsiferova, Yasunobu Okada, Ravshan Z Sabirov
The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of four other types of anion channel activated by acid, Ca(2+), patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells...
October 20, 2016: Channels
Lasse Kjær, Sabrina Cordua, Morten O Holmström, Mads Thomassen, Torben A Kruse, Niels Pallisgaard, Thomas S Larsen, Karin de Stricker, Vibe Skov, Hans C Hasselbalch
Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients...
2016: PloS One
Saura R Silva, Yani C A Diaz, Helen Alves Penha, Daniel G Pinheiro, Camila C Fernandes, Vitor F O Miranda, Todd P Michael, Alessandro M Varani
Lentibulariaceae is the richest family of carnivorous plants spanning three genera including Pinguicula, Genlisea, and Utricularia. Utricularia is globally distributed, and, unlike Pinguicula and Genlisea, has both aquatic and terrestrial forms. In this study we present the analysis of the chloroplast (cp) genome of the terrestrial Utricularia reniformis. U. reniformis has a standard cp genome of 139,725bp, encoding a gene repertoire similar to essentially all photosynthetic organisms. However, an exclusive combination of losses and pseudogenization of the plastid NAD(P)H-dehydrogenase (ndh) gene complex were observed...
2016: PloS One
Ke Ren, Wei Zhang, Xiaoqing Chen, Yingyu Ma, Yue Dai, Yimei Fan, Yayi Hou, Ren Xiang Tan, Erguang Li
The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4) as a critical player in HSV infection. We show that treatment with pan BD domain inhibitor enhanced both HSV infection. Using JQ1 as a probe, we found that JQ1, a defined BD1 inhibitor, acts through BRD4 protein since knockdown of BRD4 expression ablated JQ1 effect on HSV infection...
October 2016: PLoS Pathogens
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