Computational Predictions Provide Insights into the Biology of TAL Effector Target Sites
Identifieur interne : 001247 ( Ncbi/Merge ); précédent : 001246; suivant : 001248Computational Predictions Provide Insights into the Biology of TAL Effector Target Sites
Auteurs : Jan Grau [Allemagne] ; Annett Wolf [Allemagne] ; Maik Reschke [Allemagne] ; Ulla Bonas [Allemagne] ; Stefan Posch [Allemagne] ; Jens Boch [Allemagne]Source :
- PLoS Computational Biology [ 1553-734X ] ; 2013.
Abstract
Transcription activator-like (TAL) effectors are injected into host plant cells by
Url:
DOI: 10.1371/journal.pcbi.1002962
PubMed: 23526890
PubMed Central: 3597551
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Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Wolf, Annett" sort="Wolf, Annett" uniqKey="Wolf A" first="Annett" last="Wolf">Annett Wolf</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Reschke, Maik" sort="Reschke, Maik" uniqKey="Reschke M" first="Maik" last="Reschke">Maik Reschke</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Bonas, Ulla" sort="Bonas, Ulla" uniqKey="Bonas U" first="Ulla" last="Bonas">Ulla Bonas</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Posch, Stefan" sort="Posch, Stefan" uniqKey="Posch S" first="Stefan" last="Posch">Stefan Posch</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Boch, Jens" sort="Boch, Jens" uniqKey="Boch J" first="Jens" last="Boch">Jens Boch</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS Computational Biology</title><idno type="ISSN">1553-734X</idno><idno type="eISSN">1553-7358</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Transcription activator-like (TAL) effectors are injected into host plant cells by <italic>Xanthomonas</italic> bacteria to function as transcriptional activators for the benefit of the pathogen. The DNA binding domain of TAL effectors is composed of conserved amino acid repeat structures containing repeat-variable diresidues (RVDs) that determine DNA binding specificity. In this paper, we present TALgetter, a new approach for predicting TAL effector target sites based on a statistical model. In contrast to previous approaches, the parameters of TALgetter are estimated from training data computationally. We demonstrate that TALgetter successfully predicts known TAL effector target sites and often yields a greater number of predictions that are consistent with up-regulation in gene expression microarrays than an existing approach, Target Finder of the TALE-NT suite. We study the binding specificities estimated by TALgetter and approve that different RVDs are differently important for transcriptional activation. In subsequent studies, the predictions of TALgetter indicate a previously unreported positional preference of TAL effector target sites relative to the transcription start site. In addition, several TAL effectors are predicted to bind to the TATA-box, which might constitute one general mode of transcriptional activation by TAL effectors. Scrutinizing the predicted target sites of TALgetter, we propose several novel TAL effector virulence targets in rice and sweet orange. TAL-mediated induction of the candidates is supported by gene expression microarrays. Validity of these targets is also supported by functional analogy to known TAL effector targets, by an over-representation of TAL effector targets with similar function, or by a biological function related to pathogen infection. Hence, these predicted TAL effector virulence targets are promising candidates for studying the virulence function of TAL effectors. TALgetter is implemented as part of the open-source Java library Jstacs, and is freely available as a web-application and a command line program.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Boch, J" uniqKey="Boch J">J Boch</name></author><author><name sortKey="Bonas, U" uniqKey="Bonas U">U Bonas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boch, J" uniqKey="Boch J">J Boch</name></author><author><name sortKey="Scholze, H" uniqKey="Scholze H">H Scholze</name></author><author><name sortKey="Schornack, S" uniqKey="Schornack S">S Schornack</name></author><author><name sortKey="Landgraf, A" uniqKey="Landgraf A">A Landgraf</name></author><author><name sortKey="Hahn, S" uniqKey="Hahn S">S Hahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moscou, Mj" uniqKey="Moscou M">MJ Moscou</name></author><author><name sortKey="Bogdanove, Aj" uniqKey="Bogdanove A">AJ 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Comput Biol</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Comput. Biol</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">ploscomp</journal-id><journal-title-group><journal-title>PLoS Computational Biology</journal-title></journal-title-group><issn pub-type="ppub">1553-734X</issn><issn pub-type="epub">1553-7358</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23526890</article-id><article-id pub-id-type="pmc">3597551</article-id><article-id pub-id-type="publisher-id">PCOMPBIOL-D-12-01427</article-id><article-id pub-id-type="doi">10.1371/journal.pcbi.1002962</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Agriculture</subject><subj-group><subject>Crops</subject><subj-group><subject>Crop Diseases</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Computational Biology</subject><subj-group><subject>Molecular Genetics</subject><subj-group><subject>Gene Regulation</subject></subj-group></subj-group><subj-group><subject>Microarrays</subject><subject>Sequence Analysis</subject></subj-group></subj-group><subj-group><subject>Genetics</subject><subj-group><subject>Gene Expression</subject><subj-group><subject>DNA transcription</subject></subj-group></subj-group><subj-group><subject>Molecular Genetics</subject><subj-group><subject>Gene Regulation</subject></subj-group></subj-group><subj-group><subject>Plant Genetics</subject><subj-group><subject>Crop Genetics</subject></subj-group></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Bacterial Pathogens</subject><subject>Host-Pathogen Interaction</subject></subj-group></subj-group><subj-group><subject>Plant Science</subject><subj-group><subject>Plant Pathology</subject><subj-group><subject>Plant Pathogens</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Computer Science</subject><subj-group><subject>Computer Modeling</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Mathematics</subject><subj-group><subject>Statistics</subject><subj-group><subject>Statistical Methods</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Computational Predictions Provide Insights into the Biology of TAL Effector Target Sites</article-title><alt-title alt-title-type="running-head">Prediction of TAL Effector Targets</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Grau</surname><given-names>Jan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wolf</surname><given-names>Annett</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reschke</surname><given-names>Maik</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bonas</surname><given-names>Ulla</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Posch</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boch</surname><given-names>Jens</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Institute of Computer Science, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Genetics, Institute of Biology, Martin Luther University Halle–Wittenberg, Halle (Saale), Germany</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Tresch</surname><given-names>Achim</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Max Planck Institute for Plant Breeding Research, Germany</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>grau@informatik.uni-halle.de</email></corresp><fn fn-type="conflict"><p>I have read the journal's policy and have the following conflicts: JB and UB are part owners of a patent application regarding the use of TAL effectors.</p></fn><fn fn-type="con"><p>Implemented the software: JG AW. Conceived and designed the experiments: JG AW MR UB SP JB. Performed the experiments: MR. Analyzed the data: JG AW MR SP JB. Wrote the paper: JG SP JB.</p></fn></author-notes><pub-date pub-type="collection"><month>3</month><year>2013</year></pub-date><pmc-comment> Fake ppub added to accomodate plos workflow change from 03/2008 and 03/2009 </pmc-comment>
<pub-date pub-type="ppub"><month>3</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>14</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="ecorrected"><day>19</day><month>3</month><year>2013</year></pub-date><volume>9</volume><issue>3</issue><elocation-id>e1002962</elocation-id><history><date date-type="received"><day>5</day><month>9</month><year>2012</year></date><date date-type="accepted"><day>14</day><month>1</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Grau et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>Transcription activator-like (TAL) effectors are injected into host plant cells by <italic>Xanthomonas</italic> bacteria to function as transcriptional activators for the benefit of the pathogen. The DNA binding domain of TAL effectors is composed of conserved amino acid repeat structures containing repeat-variable diresidues (RVDs) that determine DNA binding specificity. In this paper, we present TALgetter, a new approach for predicting TAL effector target sites based on a statistical model. In contrast to previous approaches, the parameters of TALgetter are estimated from training data computationally. We demonstrate that TALgetter successfully predicts known TAL effector target sites and often yields a greater number of predictions that are consistent with up-regulation in gene expression microarrays than an existing approach, Target Finder of the TALE-NT suite. We study the binding specificities estimated by TALgetter and approve that different RVDs are differently important for transcriptional activation. In subsequent studies, the predictions of TALgetter indicate a previously unreported positional preference of TAL effector target sites relative to the transcription start site. In addition, several TAL effectors are predicted to bind to the TATA-box, which might constitute one general mode of transcriptional activation by TAL effectors. Scrutinizing the predicted target sites of TALgetter, we propose several novel TAL effector virulence targets in rice and sweet orange. TAL-mediated induction of the candidates is supported by gene expression microarrays. Validity of these targets is also supported by functional analogy to known TAL effector targets, by an over-representation of TAL effector targets with similar function, or by a biological function related to pathogen infection. Hence, these predicted TAL effector virulence targets are promising candidates for studying the virulence function of TAL effectors. TALgetter is implemented as part of the open-source Java library Jstacs, and is freely available as a web-application and a command line program.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>While it had already been discovered that transcription activator-like (TAL) effectors from <italic>Xanthomonas</italic> pathogens act as transcription factors in the host plant, deciphering the modular code of DNA binding specificity of TAL effectors in 2009 fascinated the scientific community. This modular code opens the possibility to identify virulence targets of natural TAL effectors in host plants including valuable crops. Knowing these targets deepens our understanding of the role of TAL effectors in virulence. At the same time, it is an opportunity to create resistant plants by destroying TAL effector target sites, indispensable for the pathogen, in plant genomes. However, computational methods are needed to effectively scan full genomes or promoteromes for putative target sites. Hence, we propose TALgetter, a new approach for predicting TAL effector target sites. Using TALgetter, we predict target sites of <italic>Xanthomonas</italic> TAL effectors in the important crop plants rice and sweet orange. Besides novel putative virulence targets of several TAL effectors, we also gain new insights into the biology of TAL effector targeting. The predictions of TALgetter reveal that target sites are preferentially located in the vicinity of the transcription start and that many TAL effectors bind to the TATA-box in the promoters of target genes.</p></abstract><funding-group><funding-statement>This work was supported by grants from the Deutsche Forschungsgemeinschaft (SPP 1212) and from the European Regional Development Fund of the European Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="20"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Grau, Jan" sort="Grau, Jan" uniqKey="Grau J" first="Jan" last="Grau">Jan Grau</name></noRegion><name sortKey="Boch, Jens" sort="Boch, Jens" uniqKey="Boch J" first="Jens" last="Boch">Jens Boch</name><name sortKey="Bonas, Ulla" sort="Bonas, Ulla" uniqKey="Bonas U" first="Ulla" last="Bonas">Ulla Bonas</name><name sortKey="Posch, Stefan" sort="Posch, Stefan" uniqKey="Posch S" first="Stefan" last="Posch">Stefan Posch</name><name sortKey="Reschke, Maik" sort="Reschke, Maik" uniqKey="Reschke M" first="Maik" last="Reschke">Maik Reschke</name><name sortKey="Wolf, Annett" sort="Wolf, Annett" uniqKey="Wolf A" first="Annett" last="Wolf">Annett Wolf</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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