Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans
Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the...
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| Veröffentlicht in: | Genetics (Austin) 2017-01, Vol.205 (1), p.201-219 |
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| creator | Yang, Dong-Hoon Jung, Kwang-Woo Bang, Soohyun Lee, Jang-Won Song, Min-Hee Floyd-Averette, Anna Festa, Richard A Ianiri, Giuseppe Idnurm, Alexander Thiele, Dennis J Heitman, Joseph Bahn, Yong-Sun |
| description | Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect- or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes. |
| doi_str_mv | 10.1534/genetics.116.190595 |
| format | Article |
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Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect- or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes.</description><identifier>ISSN: 1943-2631</identifier><identifier>ISSN: 0016-6731</identifier><identifier>EISSN: 1943-2631</identifier><identifier>DOI: 10.1534/genetics.116.190595</identifier><identifier>PMID: 27866167</identifier><identifier>CODEN: GENTAE</identifier><language>eng</language><publisher>United States: Genetics Society of America</publisher><subject>Cryptococcus neoformans ; Cryptococcus neoformans - genetics ; Cryptococcus neoformans - metabolism ; Cryptococcus neoformans - physiology ; Deoxyribonucleic acid ; DNA ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Fungal Proteins - genetics ; Fungal Proteins - metabolism ; Gene Expression Profiling ; Genes ; Heat Shock Transcription Factors ; Heat-Shock Proteins - genetics ; Heat-Shock Proteins - metabolism ; Heat-Shock Response - genetics ; Investigations ; Kinases ; Mammals ; Molecular Chaperones - genetics ; Molecular Chaperones - metabolism ; Oxidative stress ; Phosphorylation ; Proteins ; Rodents ; Signal Transduction ; Stress response ; Temperature ; Thermotolerance - genetics ; Thermotolerance - physiology ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcriptional Activation ; Yeast</subject><ispartof>Genetics (Austin), 2017-01, Vol.205 (1), p.201-219</ispartof><rights>Copyright © 2017 by the Genetics Society of America.</rights><rights>Copyright Genetics Society of America Jan 2017</rights><rights>Copyright © 2017 by the Genetics Society of America 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-f8e6d8e296ced5add610a501b4fdb9e8d7ec5fa9282b2b50c5efcf63ab5f971b3</citedby><cites>FETCH-LOGICAL-c532t-f8e6d8e296ced5add610a501b4fdb9e8d7ec5fa9282b2b50c5efcf63ab5f971b3</cites><orcidid>0000-0002-2902-8627 ; 0000-0001-5995-7040 ; 0000-0003-0021-5100 ; 0000-0002-5877-0812 ; 0000-0001-9563-7204 ; 0000-0002-3278-8678 ; 0000-0001-7549-0145 ; 0000-0001-9573-5752</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27866167$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Dong-Hoon</creatorcontrib><creatorcontrib>Jung, Kwang-Woo</creatorcontrib><creatorcontrib>Bang, Soohyun</creatorcontrib><creatorcontrib>Lee, Jang-Won</creatorcontrib><creatorcontrib>Song, Min-Hee</creatorcontrib><creatorcontrib>Floyd-Averette, Anna</creatorcontrib><creatorcontrib>Festa, Richard A</creatorcontrib><creatorcontrib>Ianiri, Giuseppe</creatorcontrib><creatorcontrib>Idnurm, Alexander</creatorcontrib><creatorcontrib>Thiele, Dennis J</creatorcontrib><creatorcontrib>Heitman, Joseph</creatorcontrib><creatorcontrib>Bahn, Yong-Sun</creatorcontrib><title>Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans</title><title>Genetics (Austin)</title><addtitle>Genetics</addtitle><description>Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect- or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes.</description><subject>Cryptococcus neoformans</subject><subject>Cryptococcus neoformans - genetics</subject><subject>Cryptococcus neoformans - metabolism</subject><subject>Cryptococcus neoformans - physiology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Fungal Proteins - genetics</subject><subject>Fungal Proteins - metabolism</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Heat Shock Transcription Factors</subject><subject>Heat-Shock Proteins - genetics</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>Heat-Shock Response - genetics</subject><subject>Investigations</subject><subject>Kinases</subject><subject>Mammals</subject><subject>Molecular Chaperones - genetics</subject><subject>Molecular Chaperones - metabolism</subject><subject>Oxidative stress</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Stress response</subject><subject>Temperature</subject><subject>Thermotolerance - genetics</subject><subject>Thermotolerance - physiology</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcriptional Activation</subject><subject>Yeast</subject><issn>1943-2631</issn><issn>0016-6731</issn><issn>1943-2631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkU1v1DAQhiMEoqXwC5CQJS5cdvFH7NgXJLQCilQ-BOVsOc4465LYW9uh6r_Hy7ZV4cRpPDPvvJrx0zTPCV4TztrXIwQo3uY1IWJNFOaKP2iOiWrZigpGHt57HzVPcr7AGAvF5ePmiHZSCCK642b8Blc--TCi6NB3PwYz7ZPPUK5i-pnRpzgskyn72vkW0hxLnCCZYAH5gMoW0Okym4C-mrKNdSO0Sde7Em20dskoQHQx1X5-2jxyZsrw7CaeND_evzvfnK7Ovnz4uHl7trKc0bJyEsQggSphYeBmGATBhmPSt27oFcihA8udUVTSnvYcWw7OOsFMz53qSM9OmjcH393SzzBYCCWZSe-Sn0261tF4_Xcn-K0e4y_NKWUcs2rw6sYgxcsFctGzzxamydRjlqyJFJLhVnbyP6Qt5ZwosXd9-Y_0Ii6pfvYfQ1xpUEyqih1UNsWcE7i7vQnWe-b6lrmuzPWBeZ16cf_ku5lbyOw3xs2tkg</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Yang, Dong-Hoon</creator><creator>Jung, Kwang-Woo</creator><creator>Bang, Soohyun</creator><creator>Lee, Jang-Won</creator><creator>Song, Min-Hee</creator><creator>Floyd-Averette, Anna</creator><creator>Festa, Richard A</creator><creator>Ianiri, Giuseppe</creator><creator>Idnurm, Alexander</creator><creator>Thiele, Dennis J</creator><creator>Heitman, Joseph</creator><creator>Bahn, Yong-Sun</creator><general>Genetics Society of America</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>3V.</scope><scope>4T-</scope><scope>4U-</scope><scope>7QP</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2902-8627</orcidid><orcidid>https://orcid.org/0000-0001-5995-7040</orcidid><orcidid>https://orcid.org/0000-0003-0021-5100</orcidid><orcidid>https://orcid.org/0000-0002-5877-0812</orcidid><orcidid>https://orcid.org/0000-0001-9563-7204</orcidid><orcidid>https://orcid.org/0000-0002-3278-8678</orcidid><orcidid>https://orcid.org/0000-0001-7549-0145</orcidid><orcidid>https://orcid.org/0000-0001-9573-5752</orcidid></search><sort><creationdate>20170101</creationdate><title>Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans</title><author>Yang, Dong-Hoon ; Jung, Kwang-Woo ; Bang, Soohyun ; Lee, Jang-Won ; Song, Min-Hee ; Floyd-Averette, Anna ; Festa, Richard A ; Ianiri, Giuseppe ; Idnurm, Alexander ; Thiele, Dennis J ; Heitman, Joseph ; Bahn, Yong-Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-f8e6d8e296ced5add610a501b4fdb9e8d7ec5fa9282b2b50c5efcf63ab5f971b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Cryptococcus neoformans</topic><topic>Cryptococcus neoformans - 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Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect- or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes.</abstract><cop>United States</cop><pub>Genetics Society of America</pub><pmid>27866167</pmid><doi>10.1534/genetics.116.190595</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-2902-8627</orcidid><orcidid>https://orcid.org/0000-0001-5995-7040</orcidid><orcidid>https://orcid.org/0000-0003-0021-5100</orcidid><orcidid>https://orcid.org/0000-0002-5877-0812</orcidid><orcidid>https://orcid.org/0000-0001-9563-7204</orcidid><orcidid>https://orcid.org/0000-0002-3278-8678</orcidid><orcidid>https://orcid.org/0000-0001-7549-0145</orcidid><orcidid>https://orcid.org/0000-0001-9573-5752</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1943-2631 |
| ispartof | Genetics (Austin), 2017-01, Vol.205 (1), p.201-219 |
| issn | 1943-2631 0016-6731 1943-2631 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5223503 |
| source | MEDLINE; Oxford Journals - Connect here FIRST to enable access; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Cryptococcus neoformans Cryptococcus neoformans - genetics Cryptococcus neoformans - metabolism Cryptococcus neoformans - physiology Deoxyribonucleic acid DNA DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Fungal Proteins - genetics Fungal Proteins - metabolism Gene Expression Profiling Genes Heat Shock Transcription Factors Heat-Shock Proteins - genetics Heat-Shock Proteins - metabolism Heat-Shock Response - genetics Investigations Kinases Mammals Molecular Chaperones - genetics Molecular Chaperones - metabolism Oxidative stress Phosphorylation Proteins Rodents Signal Transduction Stress response Temperature Thermotolerance - genetics Thermotolerance - physiology Transcription Factors - genetics Transcription Factors - metabolism Transcriptional Activation Yeast |
| title | Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T15%3A19%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rewiring%20of%20Signaling%20Networks%20Modulating%20Thermotolerance%20in%20the%20Human%20Pathogen%20Cryptococcus%20neoformans&rft.jtitle=Genetics%20(Austin)&rft.au=Yang,%20Dong-Hoon&rft.date=2017-01-01&rft.volume=205&rft.issue=1&rft.spage=201&rft.epage=219&rft.pages=201-219&rft.issn=1943-2631&rft.eissn=1943-2631&rft.coden=GENTAE&rft_id=info:doi/10.1534/genetics.116.190595&rft_dat=%3Cproquest_pubme%3E4306513671%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1860866201&rft_id=info:pmid/27866167&rfr_iscdi=true |