MCAF1 and Rta-activated BZLF1 transcription in Epstein-Barr virus
Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, which are involved in the transcriptional activation of EBV lytic genes. This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene p...
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| description | Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, which are involved in the transcriptional activation of EBV lytic genes. This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene promoter. In a DNA affinity precipitation assay, ATF2 was found to associate with an Rta-interacting protein, MCAF1, at the ZII element. The interaction between Rta, MCAF1, and ATF2 at the same site in the ZII region was further verified in vivo by chromatin immunoprecipitation assay. The complex appears to be crucial for the activation of BZLF1 transcription, as the overexpression of two ATF2-dominant negative mutants, or the introduction of MCAF1 siRNA into 293T cells, were both found to substantially reduce Rta-mediated transcription levels of BZLF1. Moreover, this study also found that the Rta-MCAF1-ATF2 complex binds to a typical AP-1 binding sequence on the promoter of BMRF2, a key viral gene for EBV infection. Mutation of this sequence decreased Rta-mediated promoter activity significantly. Taken together, these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription. |
| doi_str_mv | 10.1371/journal.pone.0090698 |
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This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene promoter. In a DNA affinity precipitation assay, ATF2 was found to associate with an Rta-interacting protein, MCAF1, at the ZII element. The interaction between Rta, MCAF1, and ATF2 at the same site in the ZII region was further verified in vivo by chromatin immunoprecipitation assay. The complex appears to be crucial for the activation of BZLF1 transcription, as the overexpression of two ATF2-dominant negative mutants, or the introduction of MCAF1 siRNA into 293T cells, were both found to substantially reduce Rta-mediated transcription levels of BZLF1. Moreover, this study also found that the Rta-MCAF1-ATF2 complex binds to a typical AP-1 binding sequence on the promoter of BMRF2, a key viral gene for EBV infection. Mutation of this sequence decreased Rta-mediated promoter activity significantly. Taken together, these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0090698</identifier><identifier>PMID: 24598729</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activating Transcription Factor 2 - chemistry ; Activating Transcription Factor 2 - metabolism ; Activation ; Activator protein 1 ; Amino acids ; Binding Sites ; Biology ; BZLF1 protein ; Cell Line, Tumor ; Chromatin ; Deoxyribonucleic acid ; DNA ; DNA binding proteins ; Epstein-Barr virus ; Gene expression ; Genetic aspects ; Herpesvirus 4, Human - genetics ; Humans ; Immunology ; Immunoprecipitation ; Kinases ; Laboratories ; Life sciences ; Lymphoma ; Lymphomas ; Medicine ; Membrane Glycoproteins - genetics ; Mutants ; Mutation ; Phosphorylation ; Plasmids ; Precipitation (Meteorology) ; Promoter Regions, Genetic - genetics ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Interaction Mapping ; Proteins ; Signal transduction ; siRNA ; T cells ; Trans-Activators - genetics ; Transcription (Genetics) ; Transcription activation ; Transcription Factor AP-1 - metabolism ; Transcription factors ; Transcription Factors - chemistry ; Transcription Factors - metabolism ; Transcription, Genetic ; Transcriptional Activation - genetics ; Viral Proteins - genetics ; Virology ; Viruses</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e90698-e90698</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene promoter. In a DNA affinity precipitation assay, ATF2 was found to associate with an Rta-interacting protein, MCAF1, at the ZII element. The interaction between Rta, MCAF1, and ATF2 at the same site in the ZII region was further verified in vivo by chromatin immunoprecipitation assay. The complex appears to be crucial for the activation of BZLF1 transcription, as the overexpression of two ATF2-dominant negative mutants, or the introduction of MCAF1 siRNA into 293T cells, were both found to substantially reduce Rta-mediated transcription levels of BZLF1. Moreover, this study also found that the Rta-MCAF1-ATF2 complex binds to a typical AP-1 binding sequence on the promoter of BMRF2, a key viral gene for EBV infection. Mutation of this sequence decreased Rta-mediated promoter activity significantly. Taken together, these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription.</description><subject>Activating Transcription Factor 2 - chemistry</subject><subject>Activating Transcription Factor 2 - metabolism</subject><subject>Activation</subject><subject>Activator protein 1</subject><subject>Amino acids</subject><subject>Binding Sites</subject><subject>Biology</subject><subject>BZLF1 protein</subject><subject>Cell Line, Tumor</subject><subject>Chromatin</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>Epstein-Barr virus</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunoprecipitation</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>Lymphoma</subject><subject>Lymphomas</subject><subject>Medicine</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Plasmids</subject><subject>Precipitation (Meteorology)</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Binding</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Interaction Mapping</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>T cells</subject><subject>Trans-Activators - genetics</subject><subject>Transcription (Genetics)</subject><subject>Transcription activation</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Transcription factors</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation - genetics</subject><subject>Viral Proteins - genetics</subject><subject>Virology</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYmPwDxBEQkJwkWIn_khukLpqg0pFk8bHBTfWie20rtK42E7F_v3cNZsatAvki1gnz3nt8_pNktcYTXDB8ae17V0H7WRrOz1BqEKsKp8kp7gq8ozlqHh6tD9JXni_RogWJWPPk5Oc0KrkeXWaTL_Nppc4hU6l1wEykMHsIGiVnv9exHpw0HnpzDYY26WmSy-2PmjTZefgXLozrvcvk2cNtF6_Gr5nyc_Lix-zr9ni6st8Nl1kklV5yCRXFcGsYE2NFHCkAVUKyrxsJMqVZKjAJUFaVRRzUBQTivMc13HbSI3zujhL3h50t631YpjeC0wRoaTAjERifiCUhbXYOrMBdyMsGHFXsG4pwAUjWy2iWwTKmmLKgTAq69hfNyWvaQ1cg45an4fT-nqjldRdtKIdiY7_dGYllnYniooQjveX-TAIOPun1z6IjfFSty102vZ396Y5pdGTiL77B318uoFaQhzAdI2N58q9qJgSXnLOMOKRmjxCxaX0xsgYlcbE-qjh46ghMkH_DUvovRfz79f_z179GrPvj9iVhjasvG37fZD8GCQHUDrrvdPNg8kYiX3S790Q-6SLIemx7c3xAz003Ue7uAWuCPZK</recordid><startdate>20140305</startdate><enddate>20140305</enddate><creator>Lin, Ting-Yu</creator><creator>Chu, Ya-Yun</creator><creator>Yang, Ya-Chun</creator><creator>Hsu, Shih-Wei</creator><creator>Liu, Shih-Tung</creator><creator>Chang, Li-Kwan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140305</creationdate><title>MCAF1 and Rta-activated BZLF1 transcription in Epstein-Barr virus</title><author>Lin, Ting-Yu ; Chu, Ya-Yun ; Yang, Ya-Chun ; Hsu, Shih-Wei ; Liu, Shih-Tung ; Chang, Li-Kwan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c7d941636fb0da70ea09da828fc02dc6031840ed9517ad51451221bad5fce12b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activating Transcription Factor 2 - chemistry</topic><topic>Activating Transcription Factor 2 - metabolism</topic><topic>Activation</topic><topic>Activator protein 1</topic><topic>Amino acids</topic><topic>Binding Sites</topic><topic>Biology</topic><topic>BZLF1 protein</topic><topic>Cell Line, Tumor</topic><topic>Chromatin</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA binding proteins</topic><topic>Epstein-Barr virus</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Herpesvirus 4, Human - genetics</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunoprecipitation</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Life sciences</topic><topic>Lymphoma</topic><topic>Lymphomas</topic><topic>Medicine</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Phosphorylation</topic><topic>Plasmids</topic><topic>Precipitation (Meteorology)</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Binding</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Interaction Mapping</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>siRNA</topic><topic>T cells</topic><topic>Trans-Activators - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Ting-Yu</au><au>Chu, Ya-Yun</au><au>Yang, Ya-Chun</au><au>Hsu, Shih-Wei</au><au>Liu, Shih-Tung</au><au>Chang, Li-Kwan</au><au>Mahieux, Renaud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MCAF1 and Rta-activated BZLF1 transcription in Epstein-Barr virus</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-05</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e90698</spage><epage>e90698</epage><pages>e90698-e90698</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, which are involved in the transcriptional activation of EBV lytic genes. This study sought to elucidate the mechanism by which Rta activates transcription of the Zta-encoding gene, BZLF1, through the ZII element in the gene promoter. In a DNA affinity precipitation assay, ATF2 was found to associate with an Rta-interacting protein, MCAF1, at the ZII element. The interaction between Rta, MCAF1, and ATF2 at the same site in the ZII region was further verified in vivo by chromatin immunoprecipitation assay. The complex appears to be crucial for the activation of BZLF1 transcription, as the overexpression of two ATF2-dominant negative mutants, or the introduction of MCAF1 siRNA into 293T cells, were both found to substantially reduce Rta-mediated transcription levels of BZLF1. Moreover, this study also found that the Rta-MCAF1-ATF2 complex binds to a typical AP-1 binding sequence on the promoter of BMRF2, a key viral gene for EBV infection. Mutation of this sequence decreased Rta-mediated promoter activity significantly. Taken together, these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24598729</pmid><doi>10.1371/journal.pone.0090698</doi><tpages>e90698</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activating Transcription Factor 2 - chemistry Activating Transcription Factor 2 - metabolism Activation Activator protein 1 Amino acids Binding Sites Biology BZLF1 protein Cell Line, Tumor Chromatin Deoxyribonucleic acid DNA DNA binding proteins Epstein-Barr virus Gene expression Genetic aspects Herpesvirus 4, Human - genetics Humans Immunology Immunoprecipitation Kinases Laboratories Life sciences Lymphoma Lymphomas Medicine Membrane Glycoproteins - genetics Mutants Mutation Phosphorylation Plasmids Precipitation (Meteorology) Promoter Regions, Genetic - genetics Protein Binding Protein Interaction Domains and Motifs Protein Interaction Mapping Proteins Signal transduction siRNA T cells Trans-Activators - genetics Transcription (Genetics) Transcription activation Transcription Factor AP-1 - metabolism Transcription factors Transcription Factors - chemistry Transcription Factors - metabolism Transcription, Genetic Transcriptional Activation - genetics Viral Proteins - genetics Virology Viruses |
| title | MCAF1 and Rta-activated BZLF1 transcription in Epstein-Barr virus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T19%3A41%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MCAF1%20and%20Rta-activated%20BZLF1%20transcription%20in%20Epstein-Barr%20virus&rft.jtitle=PloS%20one&rft.au=Lin,%20Ting-Yu&rft.date=2014-03-05&rft.volume=9&rft.issue=3&rft.spage=e90698&rft.epage=e90698&rft.pages=e90698-e90698&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0090698&rft_dat=%3Cgale_plos_%3EA478776107%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1504543164&rft_id=info:pmid/24598729&rft_galeid=A478776107&rft_doaj_id=oai_doaj_org_article_9064a8b5157a465cb164bf87b5ba7eae&rfr_iscdi=true |