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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/29677450/complete-programmable-decoding-of-oxidized-5-methylcytosine-nucleobases-in-dna-by-chemoselective-blockage-of-universal-tale-binders
#1
Mario Giess, Anna Witte, Julia Jasper, Oliver Koch, Daniel Summerer
5-methylcytosine (5mC) and its oxidized derivatives are regulatory elements of mammalian genomes involved in development and disease. These nucleobases do not selectively modulate Watson-Crick pairing, preventing their programmable targeting and analysis by traditional hybridiza-tion probes. Transcription-activator-like effectors (TALEs) can be engineered for use as programmable probes with epi-genetic nucleobase selectivity. However, only partial selectivi-ties for oxidized 5mC have been achieved so far, preventing unambiguous target binding...
April 20, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29677397/two-ancestral-genes-shaped-the-xanthomonas-campestris-tal-effector-gene-repertoire
#2
Nicolas Denancé, Boris Szurek, Erin L Doyle, Emmanuelle Lauber, Lisa Fontaine-Bodin, Sébastien Carrère, Endrick Guy, Ahmed Hajri, Aude Cerutti, Tristan Boureau, Stéphane Poussier, Matthieu Arlat, Adam J Bogdanove, Laurent D Noël
Xanthomonas transcription activator-like effectors (TALEs) are injected inside plant cells to promote host susceptibility by enhancing transcription of host susceptibility genes. TALE-encoding (tal) genes were thought to be absent from Brassicaceae-infecting Xanthomonas campestris (Xc) genomes based on four reference genomic sequences. We discovered tal genes in 26 of 49 Xc strains isolated worldwide and used a combination of single molecule real time (SMRT) and tal amplicon sequencing to yield a near-complete description of the TALEs found in Xc (Xc TALome)...
April 20, 2018: New Phytologist
https://www.readbyqxmd.com/read/29669249/the-transcription-factor-runx3-establishes-chromatin-accessibility-of-cis-regulatory-landscapes-that-drive-memory-cytotoxic-t-lymphocyte-formation
#3
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29666285/type-ii-secretion-dependent-aminopeptidase-lapa-and-acyltransferase-plac-are-redundant-for-nutrient-acquisition-during-legionella-pneumophila-intracellular-infection-of-amoebas
#4
Richard C White, Felizza F Gunderson, Jessica Y Tyson, Katherine H Richardson, Theo J Portlock, James A Garnett, Nicholas P Cianciotto
Legionella pneumophila genes encoding LapA, LapB, and PlaC were identified as the most highly upregulated type II secretion (T2S) genes during infection of Acanthamoeba castellanii , although these genes had been considered dispensable on the basis of the behavior of mutants lacking either lapA and lapB or plaC A plaC mutant showed even higher levels of lapA and lapB transcripts, and a lapA lapB mutant showed heightening of plaC mRNA levels, suggesting that the role of the LapA/B aminopeptidase is compensatory with respect to that of the PlaC acyltransferase...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29663926/polyethylenimine-mediated-ccr5-gene-knockout-using-transcription-activator-like-effector-nucleases
#5
Lian Jin, Yan Deng, Nongyue He, Lijun Wang, Mengling Weng
CCR5 acts as one of the key coreceptors for human immunodeficiency virus infection, which leads to acquired immune deficiency syndrome. CCR5 gene knockout comes up as an alternative method for treatment of the disease. Transcription activator-like effector nuclease is a powerful gene editing tool characterized by the ease of design, high rates of cleavage activity, and the accessibility of all ranges of transcription activator-like effector nucleases. In this study, transcription activator-like effector nuclease plasmids specifically targeting to knock out CCR5 gene were designed, constructed and then transfected to Hela and HEK293T cell lines with the assistance of the well-established gene delivery carrier polyethylenimine...
March 1, 2018: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29663920/advances-in-the-engineering-of-the-gene-editing-enzymes-and-the-genomes-understanding-and-handling-the-off-target-effects-of-crispr-cas9
#6
Yufang Yin, Qian Wang, Li Xiao, Fengjiao Wang, Zhuo Song, Cuilan Zhou, Xuan Liu, Chungen Xing, Nongyue He, Kai Li, Yan Feng, Jia Zhang
In the past decades, significant progresses have been achieved in genetic engineering of nucleases. Among the genetically engineered nucleases, zinc finger nucleases, transcription activator-like (TAL) effector nucleases, and CRIPSPR/Cas9 system form a new field of gene editing. The gene editing efficiency or targeting effect and the off-target effect are the two major determinant factors in evaluating the usefulness of a new enzyme. Engineering strategies in improving these gene editing enzymes, particularly in minimizing their off-target effects, are the focus of this paper...
March 1, 2018: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29657233/reproductive-technologies-for-the-generation-and-maintenance-of-valuable-animal-strains
#7
Takehito Kaneko
Many types of mutant and genetically engineered strains have been produced in various animal species. Their numbers have dramatically increased in recent years, with new strains being rapidly produced using genome editing techniques. In the rat, it has been difficult to produce knockout and knock-in strains because the establishment of stem cells has been insufficient. However, a large number of knockout and knock-in strains can currently be produced using genome editing techniques, including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system...
April 14, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29653269/microrna-26a-is-a-key-regulon-that-inhibits-progression-and-metastasis-of-c-myc-ezh2-double-high-advanced-hepatocellular-carcinoma
#8
Xiang Zhang, Xiao Zhang, Ting Wang, Lei Wang, Zhijun Tan, Wei Wei, Bo Yan, Jing Zhao, Kaichun Wu, Angang Yang, Rui Zhang, Lintao Jia
Overexpressed c-Myc and EZH2 usually mean high malignancy in cancers. Most of mortality from cancer is attributable to metastasis. MicroRNAs(miRNAs), like transcription factors, can regulate hundreds of genes. Here, we identify microRNA-26a (miR-26a) suppresses EZH2 and c-Myc by targeting EZH2 and CDK8 in Wnt pathway. MiR-26a is a well-known tumor-suppressive miRNA in multiple cancers, but how it is downregulated in hepatocellular carcinoma (HCC) is still unclear. Here, we disclose miR-26a is epigenetic silenced by a c-Myc-mediated PRC2-depandent way in HCC...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29652634/emerging-applications-of-genome-editing-technology-to-examine-functionality-of-gwas-associated-variants-for-complex-traits
#9
Andrew J P Smith, Panos Deloukas, Patricia B Munroe
Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo...
April 13, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29650777/-mll-leukemia-induction-by-t-9-11-chromosomal-translocation-in-human-hematopoietic-stem-cells-using-genome-editing
#10
Corina Schneidawind, Johan Jeong, Dominik Schneidawind, In-Suk Kim, Jesús Duque-Afonso, Stephen Hon Kit Wong, Masayuki Iwasaki, Erin H Breese, James L Zehnder, Matthew Porteus, Michael L Cleary
Genome editing provides a potential approach to model de novo leukemogenesis in primary human hematopoietic stem and progenitor cells (HSPCs) through induction of chromosomal translocations by targeted DNA double-strand breaks. However, very low efficiency of translocations and lack of markers for translocated cells serve as barriers to their characterization and model development. Here, we used transcription activator-like effector nucleases to generate t(9;11) chromosomal translocations encoding MLL-AF9 and reciprocal AF9-MLL fusion products in CD34+ human cord blood cells...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29649127/gene-therapy-for-chronic-hbv-can-we-eliminate-cccdna
#11
REVIEW
Kristie Bloom, Mohube Betty Maepa, Abdullah Ely, Patrick Arbuthnot
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions...
April 12, 2018: Genes
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#12
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29617316/study-of-photochemical-cytosine-to-uracil-transition-via-ultrafast-photo-cross-linking-using-vinylcarbazole-derivatives-in-duplex-dna
#13
Siddhant Sethi, Shigetaka Nakamura, Kenzo Fujimoto
Gene therapies, including genome editing, RNAi, anti-sense technology and chemical DNA editing are becoming major methods for the treatment of genetic disorders. Techniques like CRISPR-Cas9, zinc finger nuclease (ZFN) and transcription activator-like effector-based nuclease (TALEN) are a few such enzymatic techniques. Most enzymatic genome editing techniques have their disadvantages. Thus, non-enzymatic and non-invasive technologies for nucleic acid editing has been reported in this study which might possess some advantages over the older methods of DNA manipulation...
April 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29616022/temporal-regulation-of-natural-killer-t-cell-interferon-gamma-responses-by-%C3%AE-catenin-dependent-and-independent-wnt-signaling
#14
Jessica C Kling, Margaret A Jordan, Lauren A Pitt, Jana Meiners, Thao Thanh-Tran, Le Son Tran, Tam T K Nguyen, Deepak Mittal, Rehan Villani, Raymond J Steptoe, Kiarash Khosrotehrani, Stuart P Berzins, Alan G Baxter, Dale I Godfrey, Antje Blumenthal
Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29616018/induction-of-interleukin-10-producing-dendritic-cells-as-a-tool-to-suppress-allergen-specific-t-helper-2-responses
#15
REVIEW
Stefan Schülke
Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29608237/designer-nuclease-mediated-gene-correction-via-homology-directed-repair-in-an-in-vitro-model-of-canine-hemophilia-b
#16
Thorsten Bergmann, Eric Ehrke-Schulz, Jian Gao, Maren Schiwon, Verena Schildgen, Stephan David, Oliver Schildgen, Anja Ehrhardt
BACKGROUND: Gene correction at specific target loci provides a powerful strategy to overcome genetic diseases. Here we aimed at using an in vitro model for canine hemophilia B containing a single point mutation in the catalytic domain of the canine coagulation factor IX (cFIX) gene. To correct the defective gene via homology-directed repair (HDR), we designed transcription-activator like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats including Cas9 (CRISPR/Cas9) for introduction of double strand breaks at the mutation site...
April 2, 2018: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29604203/the-mirna-kallikrein-interaction-a-mosaic-of-epigenetic-regulation-in-cancer
#17
Ashley Di Meo, Cong Wang, Yufeng Cheng, Eleftherios P Diamandis, George M Yousef
The kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs have been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3' untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney, and ovarian cancers...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29603592/the-pepper-bs4c-proteins-are-localized-to-the-er-membrane-and-confer-disease-resistance-to-bacterial-blight-in-transgenic-rice
#18
Jun Wang, Xuan Zeng, Dongsheng Tian, Xiaobei Yang, Lanlan Wang, Zhongchao Yin
Transcription activator-like effector (TALE)-dependent dominant disease resistance (R) genes in plants, also referred to as executor R genes, are induced upon infection by phytopathogenic bacteria of the genus Xanthomonas harbouring the corresponding TALE genes. Unlike the traditional R proteins, the executor R proteins do not determine the resistance specificity and may function broadly in different plant species. The executor R gene Bs4C-R in the resistant genotype PI 235047 of the pepper species Capsicum pubescens (CpBs4C-R) confers disease resistance to Xanthomonas campestris pv...
March 30, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29601858/-applications-of-gene-editing-technologies-to-cellular-therapies
#19
REVIEW
Lindsay A M Rein, Haeyoon Yang, Nelson J Chao
Hematologic malignancies are characterized by genetic heterogeneity making classic gene therapy with a goal of correcting one genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9...
March 27, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29583154/comparison-of-the-editing-patterns-and-editing-efficiencies-of-talen-and-crispr-cas9-when-targeting-the-human-ccr5-gene
#20
Arildo Nerys-Junior, Luciene P Braga-Dias, Paula Pezzuto, Vinícius Cotta-de-Almeida, Amilcar Tanuri
The human C-C chemokine receptor type-5 (CCR5) is the major transmembrane co-receptor that mediates HIV-1 entry into target CD4+ cells. Gene therapy to knock-out the CCR5 gene has shown encouraging results in providing a functional cure for HIV-1 infection. In gene therapy strategies, the initial region of the CCR5 gene is a hotspot for producing functional gene knock-out. Such target gene editing can be done using programmable endonucleases such as transcription activator-like effector nucleases (TALEN) or clustered regularly interspaced short palindromic repeats (CRISPR-Cas9)...
March 19, 2018: Genetics and Molecular Biology
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