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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/28729031/knockout-of-the-urate-oxidase-gene-provides-a-stable-mouse-model-of-hyperuricemia-associated-with-metabolic-disorders
#1
Jie Lu, Xu Hou, Xuan Yuan, Lingling Cui, Zhen Liu, Xinde Li, Lidan Ma, Xiaoyu Cheng, Ying Xin, Can Wang, Keke Zhang, Xuefeng Wang, Wei Ren, Ruixia Sun, Zhaotong Jia, Zibin Tian, Qing-Sheng Mi, Changgui Li
The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28729028/micrornas-as-key-effectors-in-the-p53-network
#2
Frauke Goeman, Sabrina Strano, Giovanni Blandino
The guardian of the genome p53 is embedded in a fine-spun network of MicroRNAs. p53 is able to activate or repress directly the transcription of MicroRNAs that are participating in the tumor-suppressive mission of p53. On the other hand, the expression of p53 is under tight control of MicroRNAs that are either targeting directly p53 or factors that are modifying its protein level or activity. Although the most important function of p53 is suggested to be transcriptional regulation, there are several nontranscriptional functions described...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28715417/a-hox-complex-activates-and-potentiates-the-epidermal-growth-factor-signaling-pathway-to-specify-drosophila-oenocytes
#3
Guolun Wang, Lisa Gutzwiller, David Li-Kroeger, Brian Gebelein
Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28712502/gene-editing-with-talen-and-crispr-cas-in-rice
#4
Honghao Bi, Bing Yang
Engineered, site-specific nucleases induce genomic double-strand DNA breaks and break repair processes enable genome editing in a plethora of eukaryotic genomes. TALENs (transcription activator-like effector nucleases) and CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins) are potent biotechnological tools used for genome editing. In rice, species-tailored editing tools have proven to be efficient and easy to use. Both tools are capable of generating DNA double-strand breaks (DSBs) in vivo and such breaks can be repaired either by error-prone NHEJ (nonhomologous end joining) that leads to nucleotide insertions or deletions or by HDR (homology-directed repair) if an appropriate exogenous DNA template is provided...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28712494/crispr-cas9-based-genome-editing-in-plants
#5
Yaling Zhang, Xingliang Ma, Xianrong Xie, Yao-Guang Liu
Recently, genome editing technologies have shown great potential in plants. The newly developed clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a new generation of genome editing tool rapidly replacing the earlier zinc finger nucleases and transcription activator-like effector nucleases systems. Indeed, due to its advantages of simplicity and high efficiency, the CRISPR/Cas9-based genome editing system is becoming a powerful tool in plant science research. Here, we introduce the technical features of the plant CRISPR/Cas9-based genome editing system and its applications in plant functional genomics studies and genetic improvement...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28710417/talen-based-hpv-e7-editing-triggers-necrotic-cell-death-in-cervical-cancer-cells
#6
Sumitra Shankar, Deepti Prasad, Rahul Sanawar, Ani V Das, M Radhakrishna Pillai
Human Papillomavirus E7 and E6 oncoproteins have been considered as suitable candidate anti-viral targets since they cause malignant conversion in cervical cancers. Transcription Activator-Like Effector Nucleases (TALENs) are recent editing tools to knockout genes by inducing double stranded breaks at specific sites in the genome. In here, we have designed specific TALENs to target E7 and analyzed their efficiency in inducing cell death in cervical cancer cells. We found that designed TALENs could yield about 10-12% editing activity as observed from T7E1 and nuclease resistance assays...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705213/the-therapeutic-landscape-of-hiv-1-via-genome-editing
#7
REVIEW
Alexander Kwarteng, Samuel Terkper Ahuno, Godwin Kwakye-Nuako
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1...
July 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28698641/a-transcription-activator-like-effector-tal7-of-xanthomonas-oryzae-pv-oryzicola-activates-rice-gene-os09g29100-to-suppress-rice-immunity
#8
Lulu Cai, Yanyan Cao, Zhengyin Xu, Wenxiu Ma, Muhammad Zakria, Lifang Zou, Zaiquan Cheng, Gongyou Chen
Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo) cause bacterial leaf streak (BLS) and bacterial leaf blight (BLB) in rice, respectively. Unlike Xoo, endogenous avirulence-resistance (avr-R) gene interactions have not been identified in the Xoc-rice pathosystem; however, both pathogens possess transcription activator-like effectors (TALEs) that are known to modulate R or S genes in rice. The transfer of individual tal genes from Xoc RS105 (hypervirulent) into Xoc YNB0-17 (hypovirulent) led to the identification of tal7, which suppressed avrXa7-Xa7 mediated defense in rice containing an Xa7 R gene...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698098/development-of-a-single-cell-glxr-based-camp-biosensor-for-corynebacterium-glutamicum
#9
Julia Schulte, Meike Baumgart, Michael Bott
Cyclic adenosine monophosphate (cAMP) plays a regulatory role as second messenger in many species. In the industrial model organism Corynebacterium glutamicum, cAMP acts as effector of the global transcriptional regulator GlxR, a homolog of enterobacterial Crp. The cAMP-GlxR complex activates or represses the expression of about 200 target genes. CyaB, a membrane-bound class III adenylate cyclase, synthesizes cAMP from ATP, but another yet unknown cAMP-forming enzyme is likely present in C. glutamicum. Recently, we identified the cAMP phosphodiesterase CpdA, which catalyzes the conversion of cAMP to AMP...
July 8, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28681201/gene-editing-tools-state-of-the-art-and-the-road-ahead-for-the-model-and-non-model-fishes
#10
REVIEW
Hirak Kumar Barman, Kiran Dashrath Rasal, Vemulawada Chakrapani, A S Ninawe, Doyil T Vengayil, Syed Asrafuzzaman, Jitendra K Sundaray, Pallipuram Jayasankar
Advancements in the DNA sequencing technologies and computational biology have revolutionized genome/transcriptome sequencing of non-model fishes at an affordable cost. This has led to a paradigm shift with regard to our heightened understandings of structure-functional relationships of genes at a global level, from model animals/fishes to non-model large animals/fishes. Whole genome/transcriptome sequencing technologies were supplemented with the series of discoveries in gene editing tools, which are being used to modify genes at pre-determined positions using programmable nucleases to explore their respective in vivo functions...
July 5, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28676762/personalized-or-precision-medicine-the-example-of-cystic-fibrosis
#11
REVIEW
Fernando A L Marson, Carmen S Bertuzzo, José D Ribeiro
The advent of the knowledge on human genetics, by the identification of disease-associated variants, culminated in the understanding of human variability. With the genetic knowledge, the specificity of the clinical phenotype and the drug response of each individual were understood. Using the cystic fibrosis (CF) as an example, the new terms that emerged such as personalized medicine and precision medicine can be characterized. The genetic knowledge in CF is broad and the presence of a monogenic disease caused by mutations in the CFTR gene enables the phenotype-genotype association studies (including the response to drugs), considering the wide clinical and laboratory spectrum dependent on the mutual action of genotype, environment, and lifestyle...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28674932/use-of-transcription-activator-like-effector-for-efficient-gene-modification-and-transcription-in-the-filamentous-fungus-trichoderma-reesei
#12
Pei Liu, Wei Wang, Dongzhi Wei
Filamentous fungi have wide applications in the field of biotechnology. The use of transcription activator-like effectors (TALEs) is a powerful genome-engineering tool, which can facilitate genome editing and transcriptional modulation, and has been used for genetic modification in a variety of organisms. However, a transcription activator-like effectors nuclease (TALEN) approach has not been used in filamentous fungi so far. Here, we aimed to establish the shortest TALEN and TALE-transcription factor (TALE-TF) proteins for use in gene modification and transcription in the filamentous fungus Trichoderma reesei...
July 3, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28667437/an-elf2-like-transcription-factor-acts-as-repressor-of-the-mouse-ecto-5-nucleotidase-gene-expression-in-hepatic-myofibroblasts
#13
Michel Fausther, Elise G Lavoie, Jessica R Goree, Jonathan A Dranoff
Hepatic fibrosis represents a pathological wound healing and tissue repair process triggered in response to chronic liver injury. A heterogeneous population of activated non-parenchymal liver cells, known as liver myofibroblasts, functions as the effector cells in hepatic fibrosis. Upon activation, liver myofibroblasts become fibrogenic, acquiring contractile properties and increasing collagen production capacity, while developing enhanced sensitivity to endogenous molecules and factors released in the local microenvironment...
June 30, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28666954/1700012b09rik-a-foxj1-effector-gene-active-in-ciliated-tissues-of-the-mouse-but-not-essential-for-motile-ciliogenesis
#14
Michael Stauber, Karsten Boldt, Christoph Wrede, Marina Weidemann, Manuela Kellner, Karin Schuster-Gossler, Mark Philipp Kühnel, Jan Hegermann, Marius Ueffing, Achim Gossler
In humans and mice, motile cilia occur on the surface of the embryonic ventral node, on respiratory and ependymal epithelia and in reproductive organs where they ensure normal left-right asymmetry of the organism, mucociliary clearance of airways, homeostasis of the cerebrospinal fluid and fertility. The genetic programme for the formation of motile cilia, thus critical for normal development and health, is switched on by the key transcription factor FOXJ1. In previous microarray screens for murine FOXJ1 effectors, we identified candidates for novel factors involved in motile ciliogenesis, including both genes that are well conserved throughout metazoa and beyond, like FOXJ1 itself, and genes without overt homologues outside higher vertebrates...
June 28, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28666380/comparative-analysis-of-chimeric-zfp-tale-and-cas9-piggybac-transposases-for-integration-into-a-single-locus-in-human-cells
#15
Wentian Luo, Daniel L Galvan, Lauren E Woodard, Dan Dorset, Shawn Levy, Matthew H Wilson
Integrating DNA delivery systems hold promise for many applications including treatment of diseases; however, targeted integration is needed for improved safety. The piggyBac (PB) transposon system is a highly active non-viral gene delivery system capable of integrating defined DNA segments into host chromosomes without requiring homologous recombination. We systematically compared four different engineered zinc finger proteins (ZFP), four transcription activator-like effector proteins (TALE), CRISPR associated protein 9 (SpCas9) and the catalytically inactive dSpCas9 protein fused to the amino-terminus of the transposase enzyme designed to target the hypoxanthine phosphoribosyltransferase (HPRT) gene located on human chromosome X...
June 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28664195/partial-exhaustion-of-cd8-t-cells-and-clinical-response-to-teplizumab-in-new-onset-type-1-diabetes
#16
S Alice Long, Jerill Thorpe, Hannah A DeBerg, Vivian Gersuk, James Eddy, Kristina M Harris, Mario Ehlers, Kevan C Herold, Gerald T Nepom, Peter S Linsley
Biologic treatment of T1D typically results in transient stabilization of C-peptide levels (a surrogate for endogenous insulin secretion) in some patients, followed by progression at the same rate as in untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody teplizumab. We identified a population of CD8 T cells that accumulated in subjects with the best response to treatment (responders) and showed that these cells phenotypically resembled exhausted T cells by expressing high levels of the transcription factor EOMES, effector molecules, and multiple inhibitory receptors (IRs), including TIGIT and KLRG1...
November 2016: Science Immunology
https://www.readbyqxmd.com/read/28656232/transcription-factor-7-like-2-promotes-oligodendrocyte-differentiation-and-remyelination
#17
Chao Weng, Man Ding, Shanghua Fan, Qian Cao, Zuneng Lu
Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination. In order to clarify this, in situ hybridization, immunofluorescence and western blot analysis using in vivo TCF7L2 conditional knockout mice, were performed and it was found that TCF7L2 promotes oligodendrocyte differentiation during myelin formation and remyelination...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28655470/keratinocytes-in-atopic-dermatitis-express-abundant-%C3%AE-np73-regulating-thymic-stromal-lymphopoietin-production-via-nf-%C3%AE%C2%BAb
#18
Ayako Kumagai, Terufumi Kubo, Koji Kawata, Ryuta Kamekura, Keiji Yamashita, Sumito Jitsukawa, Tomonori Nagaya, Yasuyuki Sumikawa, Tetsuo Himi, Toshiharu Yamashita, Shingo Ichimiya
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that often cannot be completely controlled by modern medicine. Since multiple factors are intricately involved in the pathogenesis of AD, wide-ranging research is required for further advancement of AD treatment. Epidermal keratinocytes are the forefront to the external environment and play a pivotal role in the initiation of immune reaction against exogenous invasion. OBJECTIVE: Thymic stromal lymphopoietin (TSLP) is a keratinocyte-derived cytokine that induces differentiation and activation of type 2 helper T cells and innate lymphoid cells, cardinal effectors in pathophysiology of AD...
June 22, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28652310/bacterial-nucleotidyl-cyclase-inhibits-host-innate-immune-response-through-suppressing-tak1-activation
#19
Chenxi He, Yilong Zhou, Feng Liu, Haipeng Liu, Hao Tan, Shouguang Jin, Weihui Wu, Baoxue Ge
Exoenzyme Y (ExoY) is a type III secretion system effector found in 90% of the Pseudomonas aeruginosa isolates. Although it is known that ExoY is a soluble nucleotidyl cyclase that increases the cytoplasmic levels of nucleoside 3' , 5' -cyclic monophosphates (cNMPs) to mediate endothelial Tau phosphorylation and permeability, its functional role in the innate immune response is still poorly understood. Transforming growth factor β activated kinase-1 (TAK1) is critical for mediating Toll-like receptor (TLR) signaling and subsequent activation of NF-κB and AP-1, which are transcriptional activators of innate immunity...
June 26, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28651004/a-human-endogenous-retrovirus-derived-gene-that-can-contribute-to-oncogenesis-by-activating-the-erk-pathway-and-inducing-migration-and-invasion
#20
Cécile Lemaître, Jhen Tsang, Caroline Bireau, Thierry Heidmann, Marie Dewannieux
Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected...
June 2017: PLoS Pathogens
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