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Browsing by Author "Yu, Jun"

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    Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling
    Zhang, Yonggang; Arango-Argoty, Gustavo; Li, Fang; Xiao, Xiao; Putatunda, Raj; Yu, Jun; Yang, Xiao-Feng; Wang, Hong; Watson, Layne T.; Zhang, Liqing; Hu, Wenhui (2018-09-10)
    Background CRISPR/CAS9 (epi)genome editing revolutionized the field of gene and cell therapy. Our previous study demonstrated that a rapid and robust reactivation of the HIV latent reservoir by a catalytically-deficient Cas9 (dCas9)-synergistic activation mediator (SAM) via HIV long terminal repeat (LTR)-specific MS2-mediated single guide RNAs (msgRNAs) directly induces cellular suicide without additional immunotherapy. However, potential off-target effect remains a concern for any clinical application of Cas9 genome editing and dCas9 epigenome editing. After dCas9 treatment, potential off-target responses have been analyzed through different strategies such as mRNA sequence analysis, and functional screening. In this study, a comprehensive analysis of the host transcriptome including mRNA, lncRNA, and alternative splicing was performed using human cell lines expressing dCas9-SAM and HIV-targeting msgRNAs. Results The control scrambled msgRNA (LTR_Zero), and two LTR-specific msgRNAs (LTR_L and LTR_O) groups show very similar expression profiles of the whole transcriptome. Among 839 identified lncRNAs, none exhibited significantly different expression in LTR_L vs. LTR_Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were significantly decreased. Among 142,791 mRNAs, four genes were differentially expressed in LTR_L vs. LTR_Zero group. There were 21 genes significantly downregulated in LTR_O vs. either LTR_Zero or LTR_L group and one third of them are histone related. The distributions of different types of alternative splicing were very similar either within or between groups. There were no apparent changes in all the lncRNA and mRNA transcripts between the LTR_L and LTR_Zero groups. Conclusion This is an extremely comprehensive study demonstrating the rare off-target effects of the HIV-specific dCas9-SAM system in human cells. This finding is encouraging for the safe application of dCas9-SAM technology to induce target-specific reactivation of latent HIV for an effective “shock-and-kill” strategy.
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    One thousand plant transcriptomes and the phylogenomics of green plants
    Leebens-Mack, James H.; Barker, Michael S.; Carpenter, Eric J.; Deyholos, Michael K.; Gitzendanner, Matthew A.; Graham, Sean W.; Grosse, Ivo; Li, Zheng; Melkonian, Michael; Mirarab, Siavash; Porsch, Martin; Quint, Marcel; Rensing, Stefan A.; Soltis, Douglas E.; Soltis, Pamela S.; Stevenson, Dennis W.; Ullrich, Kristian K.; Wickett, Norman J.; DeGironimo, Lisa; Edger, Patrick P.; Jordon-Thaden, Ingrid E.; Joya, Steve; Liu, Tao; Melkonian, Barbara; Miles, Nicholas W.; Pokorny, Lisa; Quigley, Charlotte; Thomas, Philip; Villarreal, Juan Carlos; Augustin, Megan M.; Barrett, Matthew D.; Baucom, Regina S.; Beerling, David J.; Benstein, Ruben Maximilian; Biffin, Ed; Brockington, Samuel F.; Burge, Dylan O.; Burris, Jason N.; Burris, Kellie P.; Burtet-Sarramegna, Valerie; Caicedo, Ana L.; Cannon, Steven B.; Cebi, Zehra; Chang, Ying; Chater, Caspar; Cheeseman, John M.; Chen, Tao; Clarke, Neil D.; Clayton, Harmony; Covshoff, Sarah; Crandall-Stotler, Barbara J.; Cross, Hugh; dePamphilis, Claude W.; Der, Joshua P.; Determann, Ron; Dickson, Rowan C.; Di Stilio, Veronica S.; Ellis, Shona; Fast, Eva; Feja, Nicole; Field, Katie J.; Filatov, Dmitry A.; Finnegan, Patrick M.; Floyd, Sandra K.; Fogliani, Bruno; Garcia, Nicolas; Gateble, Gildas; Godden, Grant T.; Goh, Falicia (Qi Yun); Greiner, Stephan; Harkess, Alex; Heaney, James Mike; Helliwell, Katherine E.; Heyduk, Karolina; Hibberd, Julian M.; Hodel, Richard G. J.; Hollingsworth, Peter M.; Johnson, Marc T. J.; Jost, Ricarda; Joyce, Blake; Kapralov, Maxim V.; Kazamia, Elena; Kellogg, Elizabeth A.; Koch, Marcus A.; Von Konrat, Matt; Konyves, Kalman; Kutchan, Toni M.; Lam, Vivienne; Larsson, Anders; Leitch, Andrew R.; Lentz, Roswitha; Li, Fay-Wei; Lowe, Andrew J.; Ludwig, Martha; Manos, Paul S.; Mavrodiev, Evgeny; McCormick, Melissa K.; McKain, Michael; McLellan, Tracy; McNeal, Joel R.; Miller, Richard E.; Nelson, Matthew N.; Peng, Yanhui; Ralph, Paula E.; Real, Daniel; Riggins, Chance W.; Ruhsam, Markus; Sage, Rowan F.; Sakai, Ann K.; Scascitella, Moira; Schilling, Edward E.; Schlosser, Eva-Marie; Sederoff, Heike; Servick, Stein; Sessa, Emily B.; Shaw, A. Jonathan; Shaw, Shane W.; Sigel, Erin M.; Skema, Cynthia; Smith, Alison G.; Smithson, Ann; Stewart, C. Neal, Jr.; Stinchcombe, John R.; Szovenyi, Peter; Tate, Jennifer A.; Tiebel, Helga; Trapnell, Dorset; Villegente, Matthieu; Wang, Chun-Neng; Weller, Stephen G.; Wenzel, Michael; Weststrand, Stina; Westwood, James H.; Whigham, Dennis F.; Wu, Shuangxiu; Wulff, Adrien S.; Yang, Yu; Zhu, Dan; Zhuang, Cuili; Zuidof, Jennifer; Chase, Mark W.; Pires, J. Chris; Rothfels, Carl J.; Yu, Jun; Chen, Cui; Chen, Li; Cheng, Shifeng; Li, Juanjuan; Li, Ran; Li, Xia; Lu, Haorong; Ou, Yanxiang; Sun, Xiao; Tan, Xuemei; Tang, Jingbo; Tian, Zhijian; Wang, Feng; Wang, Jun; Wei, Xiaofeng; Xu, Xun; Yan, Zhixiang; Yang, Fan; Zhong, Xiaoni; Zhou, Feiyu; Zhu, Ying; Zhang, Yong; Ayyampalayam, Saravanaraj; Barkman, Todd J.; Nam-Phuong Nguyen; Matasci, Naim; Nelson, David R.; Sayyari, Erfan; Wafula, Eric K.; Walls, Ramona L.; Warnow, Tandy; An, Hong; Arrigo, Nils; Baniaga, Anthony E.; Galuska, Sally; Jorgensen, Stacy A.; Kidder, Thomas I.; Kong, Hanghui; Lu-Irving, Patricia; Marx, Hannah E.; Qi, Xinshuai; Reardon, Chris R.; Sutherland, Brittany L.; Tiley, George P.; Welles, Shana R.; Yu, Rongpei; Zhan, Shing; Gramzow, Lydia; Theissen, Gunter; Wong, Gane Ka-Shu (2019-10-31)
    Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.