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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/29228103/fertility-impairment-with-defective-spermatogenesis-and-steroidogenesis-in-male-zebrafish-lacking-androgen-receptor
#1
Haipei Tang, Yu Chen, Le Wang, Yike Yin, Gaofei Li, Yin Guo, Yun Liu, Haoran Lin, Christopher H K Cheng, Xiaochun Liu
The pivotal role of androgen receptor (AR) in regulating male fertility has attracted much research attention in the past two decades. Previous studies have shown that total androgen receptor knockout would lead to incomplete spermatogenesis and a lowered serum testosterone levels in mice, resulting in azoospermia and infertility. However, the precise physiological role of ar in controlling fertility of male fish is still poorly understood. In this study, we have established an ar knockout zebrafish line by transcription activator-like effectors nucleases (TALENs)...
December 6, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29216270/generation-and-characterization-of-kctd15-mutations-in-zebrafish
#2
Alison Heffer, Gregory D Marquart, Allisan Aquilina-Beck, Nabil Saleem, Harold A Burgess, Igor B Dawid
Potassium channel tetramerization domain containing 15 (Kctd15) was previously found to have a role in early neural crest (NC) patterning, specifically delimiting the region where NC markers are expressed via repression of transcription factor AP-2a and inhibition of Wnt signaling. We used transcription activator-like effector nucleases (TALENs) to generate null mutations in zebrafish kctd15a and kctd15b paralogs to study the in vivo role of Kctd15. We found that while deletions producing frame-shift mutations in each paralog showed no apparent phenotype, kctd15a/b double mutant zebrafish are smaller in size and show several phenotypes including some affecting the NC, such as expansion of the early NC domain, increased pigmentation, and craniofacial defects...
2017: PloS One
https://www.readbyqxmd.com/read/29213081/pak2-is-essential-for-the-function-of-foxp3-regulatory-t-cells-through-maintaining-a-suppressive-treg-phenotype
#3
Kyle L O'Hagan, Stephen D Miller, Hyewon Phee
Foxp3, a key transcription factor that drives lineage differentiation of regulatory T cells (Tregs), was thought to imprint a unique and irreversible genetic signature within Tregs. Recent evidence, however, suggests that loss or attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector T cells capable of producing proinflammatory cytokines. Herein, we report that the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining Treg stability and suppressive function...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29208373/roles-of-maternal-wnt8a-transcripts-in-axis-formation-in-zebrafish
#4
Hiromu Hino, Akiko Nakanishi, Ryoko Seki, Tsubasa Aoki, Etsuro Yamaha, Atsuo Kawahara, Takashi Shimizu, Masahiko Hibi
In early zebrafish development, the program for dorsal axis formation begins soon after fertilization. Previous studies suggested that dorsal determinants (DDs) localize to the vegetal pole, and are transported to the dorsal blastomeres in a microtubule-dependent manner. The DDs activate the canonical Wnt pathway and induce dorsal-specific genes that are required for dorsal axis formation. Among wnt-family genes, only the wnt8a mRNA is reported to localize to the vegetal pole in oocytes and to induce the dorsal axis, suggesting that Wnt8a is a candidate DD...
December 2, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29206103/a-population-of-innate-myelolymphoblastoid-effector-cell-expanded-by-inactivation-of-mtor-complex-1-in-mice
#5
Fei Tang, Peng Zhang, Peiying Ye, Christopher A Lazarski, Qi Wu, Ingrid L Bergin, Timothy P Bender, Michael N Hall, Ya Cui, Liguo Zhang, Taijiao Jiang, Yang Liu, Pan Zheng
Adaptive autoimmunity is restrained by controlling population sizes and pathogenicity of harmful clones, while innate destruction is controlled at effector phase. We report here that deletion of Rptor in mouse hematopoietic stem/progenitor cells causes self-destructive innate immunity by massively increasing the population of previously uncharacterized innate myelolymphoblastoid effector cells (IMLECs). Mouse IMLECs are CD3-B220-NK1.1-Ter119- CD11clow/-CD115-F4/80low/-Gr-1- CD11b+, but surprisingly express high levels of PD-L1...
December 5, 2017: ELife
https://www.readbyqxmd.com/read/29203573/mechanisms-of-%C3%AE-cell-dedifferentiation-in-diabetes-recent-findings-and-future-research-directions
#6
Mohammed Bensellam, Jean-Christophe Jonas, D Ross Laybutt
Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state...
December 4, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#7
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29197638/robust-transcriptional-activation-in-plants-using-multiplexed-crispr-act2-0-and-mtale-act-systems
#8
Levi G Lowder, Jianping Zhou, Yingxiao Zhang, Aimee Malzahn, Zhaohui Zhong, Tzung-Fu Hsieh, Daniel F Voytas, Yong Zhang, Yiping Qi
Previously, we have shown transcriptional activation of endogenous genes in plants using dCas9-VP64. Here, we develop a second generation of vector systems for enhanced transcriptional activation in plants. We tested multiple strategies for CRISPR-Cas9 based transcriptional activation. Simultaneous recruitment of VP64 by dCas9 and a modified guide RNA scaffold gRNA2.0 (designated CRISPR-Act2.0) yielded stronger transcriptional activation than our first generation dCas9-VP64 activators. In addition, we have built a multiplex transcription activator-like effector activation (mTALE-Act) system for simultaneous activation of up to four genes in plants...
November 29, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29196300/mettl3-mutation-disrupts-gamete-maturation-and-reduces-fertility-in-zebrafish
#9
Hui Xia, Chengrong Zhong, Xingxing Wu, Ji Chen, Binbin Tao, Xiaoqin Xia, Mijuan Shi, Zuoyan Zhu, Vance L Trudeau, Wei Hu
N6-methyladenosine (m6A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic mRNA. Previous studies have implicated m6A modification in multiple biological processes, but the in vivo function of m6A has been difficult to study, because mettl3 mutants are embryonic lethal in both mammals and plants. In this study, we have used transcription activator-like effector nucleases and generated viable zygotic mettl3 mutant, Zmettl3m/m , in zebrafish. We find that the oocytes in Zmettl3m/m adult females are stalled in early development and the ratio of full grown stage (FG) follicles is significantly lower than that of wild type...
December 1, 2017: Genetics
https://www.readbyqxmd.com/read/29187589/stat5b-a-differential-regulator-of-the-life-and-death-of-cd4-effector-memory-t-cells
#10
Sonia S Majri, Jill M Fritz, Alejandro V Villarino, Lixin Zheng, Chrysi Kanellopoulou, Benjamin Chaigne-Delalande, Juha Grönholm, Julie E Niemela, Behdad Afzali, Matthew Biancalana, Stefania Pittaluga, Ashleigh Sun, José L Cohen, Steven M Holland, John J O'Shea, Gulbu Uzel, Michael J Lenardo
Understanding the control of Ag restimulation-induced T cell death (RICD), especially in cancer immunotherapy, where highly proliferating T cells will encounter potentially large amounts of tumor Ags, is important now more than ever. It has been known that growth cytokines make T cells susceptible to RICD, but the precise molecular mediators that govern this in T cell subsets is unknown until now. STAT proteins are a family of transcription factors that regulate gene expression programs underlying key immunological processes...
November 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29186020/applications-of-alternative-nucleases-in-the-age-of-crispr-cas9
#11
REVIEW
Tuhin K Guha, David R Edgell
Breakthroughs in the development of programmable site-specific nucleases, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and most recently, the clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (including Cas9) have greatly enabled and accelerated genome editing. By targeting double-strand breaks to user-defined locations, the rates of DNA repair events are greatly enhanced relative to un-catalyzed events at the same sites...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29181004/identification-of-secretory-leukoprotease-inhibitor-as-an-endogenous-negative-regulator-in-allergic-effector-cells
#12
Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura
Mast cells, basophils, and eosinophils are central effectors in allergic inflammatory disorders. These cells secrete abundant serine proteases as well as chemical mediators and cytokines; however, the expression profiles and functions of their endogenous inhibitors remain elusive. We found that murine secretory leukoprotease inhibitor (SLPI) is expressed in basophils and eosinophils but in not in mast cells. SLPI-deficient (Slpi-/-) basophils produce more cytokines than wild-type mice after IgE stimulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29170655/the-tal-effector-avrbs3-from-xanthomonas-campestris-pv-vesicatoria-contains-multiple-export-signals-and-can-enter-plant-cells-in-the-absence-of-the-type-iii-secretion-translocon
#13
Felix Scheibner, Sylvestre Marillonnet, Daniela Büttner
Pathogenicity of the Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria depends on a type III secretion (T3S) system which translocates effector proteins into plant cells. Effector protein delivery is controlled by the T3S chaperone HpaB, which presumably escorts effector proteins to the secretion apparatus. One intensively studied effector is the transcription activator-like (TAL) effector AvrBs3, which binds to promoter sequences of plant target genes and activates plant gene expression...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29166645/angiotensin-ii-infusion-does-not-cause-abdominal-aortic-aneurysms-in-apolipoprotein-e-deficient-rats
#14
Evan H Phillips, Mandy S Chang, Sydney Gorman, Hamna J Qureshi, Karin F K Ejendal, Tamara L Kinzer-Ursem, A Nicole Blaize, Craig J Goergen
The apolipoprotein E-deficient (apoE-/-) mouse model has advanced our understanding of cardiovascular disease mechanisms and experimental therapeutics. This spontaneous model recapitulates aspects of human atherosclerosis, and allows for the development of dissecting abdominal aortic aneurysms (AAAs) when combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE gene using transcription activator-like effector nucleases...
November 23, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/29163628/a-conserved-basal-transcription-factor-is-required-for-the-function-of-diverse-tal-effectors-in-multiple-plant-hosts
#15
Renyan Huang, Shugang Hui, Meng Zhang, Pei Li, Jinghua Xiao, Xianghua Li, Meng Yuan, Shiping Wang
Many Xanthomonas bacteria use transcription activator-like effector (TALE) proteins to activate plant disease susceptibility (S) genes, and this activation contributes to disease. We recently reported that rice basal transcription factor IIA gamma subunit, OsTFIIAγ5, is hijacked by TALE-carrying Xanthomonas oryzae infecting the plants. However, whether TFIIAγs are also involved in TALE-carrying Xanthomonas-caused diseases in other plants is unknown. Here, molecular and genetic approaches were used to investigate the role of TFIIAγs in other plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29163605/the-verticillium-dahliae-snodprot1-like-protein-vdcp1-contributes-to-virulence-and-triggers-the-plant-immune-system
#16
Yi Zhang, Yuhan Gao, Yingbo Liang, Yijie Dong, Xiufen Yang, Jingjing Yuan, Dewen Qiu
During pathogenic infection, hundreds of proteins that play vital roles in the Verticillium dahliae-host interaction are secreted. In this study, an integrated proteomic analysis of secreted V. dahliae proteins was performed, and a conserved secretory protein, designated VdCP1, was identified as a member of the SnodProt1 phytotoxin family. An expression analysis of the vdcp1 gene revealed that the transcript is present in every condition studied and displays elevated expression throughout the infection process...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29162808/a-multiplexable-tale-based-binary-expression-system-for-in-vivo-cellular-interaction-studies
#17
Markus Toegel, Ghows Azzam, Eunice Y Lee, David J H F Knapp, Ying Tan, Ming Fa, Tudor A Fulga
Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158545/a-potent-cas9-derived-gene-activator-for-plant-and-mammalian-cells
#18
Zhenxiang Li, Dandan Zhang, Xiangyu Xiong, Bingyu Yan, Wei Xie, Jen Sheen, Jian-Feng Li
Overexpression of complementary DNA represents the most commonly used gain-of-function approach for interrogating gene functions and for manipulating biological traits. However, this approach is challenging and inefficient for multigene expression due to increased labour for cloning, limited vector capacity, requirement of multiple promoters and terminators, and variable transgene expression levels. Synthetic transcriptional activators provide a promising alternative strategy for gene activation by tethering an autonomous transcription activation domain (TAD) to an intended gene promoter at the endogenous genomic locus through a programmable DNA-binding module...
November 20, 2017: Nature Plants
https://www.readbyqxmd.com/read/29157536/a-comparison-of-techniques-to-evaluate-the-effectiveness-of-genome-editing
#19
REVIEW
Diego Germini, Tatiana Tsfasman, Vlada V Zakharova, Nikolajs Sjakste, Marс Lipinski, Yegor Vassetzky
Genome editing using engineered nucleases (meganucleases, zinc finger nucleases, transcription activator-like effector nucleases) has created many recent breakthroughs. Prescreening for efficiency and specificity is a critical step prior to using any newly designed genome editing tool for experimental purposes. The current standard screening methods of evaluation are based on DNA sequencing or use mismatch-sensitive endonucleases. They can be time-consuming and costly or lack reproducibility. Here, we review and critically compare standard techniques with those more recently developed in terms of reliability, time, cost, and ease of use...
November 17, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#20
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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