STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus
Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction...
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| Veröffentlicht in: | The Journal of biological chemistry 2004-02, Vol.279 (8), p.7339-7345 |
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| container_title | The Journal of biological chemistry |
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| creator | O'Sullivan, Audrey Chang, Hua-Chen Yu, Qing Kaplan, Mark H. |
| description | Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor α chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene. |
| doi_str_mv | 10.1074/jbc.M309979200 |
| format | Article |
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Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor α chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M309979200</identifier><identifier>PMID: 14660657</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Northern ; CD25 antigen ; Cell Membrane - metabolism ; Cell Separation ; Chromatin - metabolism ; CREB-Binding Protein ; DNA-Binding Proteins - metabolism ; DNA-Binding Proteins - physiology ; Flow Cytometry ; Histones - metabolism ; Interleukin-12 - metabolism ; Mice ; Mice, Inbred BALB C ; Models, Biological ; Nuclear Proteins - metabolism ; Polymerase Chain Reaction ; Precipitin Tests ; Promoter Regions, Genetic ; Protein Binding ; Receptors, Interleukin-2 - biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Spleen - cytology ; STAT4 protein ; STAT4 Transcription Factor ; Time Factors ; Trans-Activators - metabolism ; Trans-Activators - physiology ; Transcription, Genetic</subject><ispartof>The Journal of biological chemistry, 2004-02, Vol.279 (8), p.7339-7345</ispartof><rights>2004 © 2004 ASBMB. 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Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor α chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene.</description><subject>Animals</subject><subject>Blotting, Northern</subject><subject>CD25 antigen</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Separation</subject><subject>Chromatin - metabolism</subject><subject>CREB-Binding Protein</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Flow Cytometry</subject><subject>Histones - metabolism</subject><subject>Interleukin-12 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Models, Biological</subject><subject>Nuclear Proteins - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Precipitin Tests</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Receptors, Interleukin-2 - biosynthesis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Spleen - cytology</subject><subject>STAT4 protein</subject><subject>STAT4 Transcription Factor</subject><subject>Time Factors</subject><subject>Trans-Activators - metabolism</subject><subject>Trans-Activators - physiology</subject><subject>Transcription, Genetic</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFr3DAQRkVJabZprz0Wk0Nv3o4sWZaPYZM2C1sKzRZ6E7I0ipXaViLZCf33VdmFnELnMjDzZvh4hHygsKbQ8M93nVl_Y9C2TVsBvCIrCpKVrKa_TsgKoKJlW9XylLxN6Q5y8Za-IaeUCwGiblbk5mZ_sefFNhU_8GHxEW3hQiy204xxwOW3n0palX6yi8mrTR_DqGc_ZXoMFgc_3RbBFXOPxeayqotdMEt6R147PSR8f-xn5OeXq_3mutx9_7rdXOxKw5mcS2cay3IebQXj1DoGBlvBsZMA2hnmHJdaWN0BuppK4UylG94B7ZzME8POyKfD3_sYHhZMsxp9MjgMesKwJCWBCkYb_l-QZkdcgsjg-gCaGFKK6NR99KOOfxQF9c-3yr7Vs-988PH4eelGtM_4UXAGzg9A72_7p-xXdT6YHkdVNa2SqmGszZA8QJhtPXqMKhmPUzaeD8ysbPAvBfgLtpWYyQ</recordid><startdate>20040220</startdate><enddate>20040220</enddate><creator>O'Sullivan, Audrey</creator><creator>Chang, Hua-Chen</creator><creator>Yu, Qing</creator><creator>Kaplan, Mark H.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040220</creationdate><title>STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus</title><author>O'Sullivan, Audrey ; Chang, Hua-Chen ; Yu, Qing ; Kaplan, Mark H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-fc7d3491ad6341df30ce964eb800afc3ff48a6dab0ef5186fc2a74b01bf8ef5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Blotting, Northern</topic><topic>CD25 antigen</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Separation</topic><topic>Chromatin - metabolism</topic><topic>CREB-Binding Protein</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Flow Cytometry</topic><topic>Histones - metabolism</topic><topic>Interleukin-12 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Models, Biological</topic><topic>Nuclear Proteins - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Precipitin Tests</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>Receptors, Interleukin-2 - biosynthesis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Spleen - cytology</topic><topic>STAT4 protein</topic><topic>STAT4 Transcription Factor</topic><topic>Time Factors</topic><topic>Trans-Activators - metabolism</topic><topic>Trans-Activators - physiology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'Sullivan, Audrey</creatorcontrib><creatorcontrib>Chang, Hua-Chen</creatorcontrib><creatorcontrib>Yu, Qing</creatorcontrib><creatorcontrib>Kaplan, Mark H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'Sullivan, Audrey</au><au>Chang, Hua-Chen</au><au>Yu, Qing</au><au>Kaplan, Mark H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2004-02-20</date><risdate>2004</risdate><volume>279</volume><issue>8</issue><spage>7339</spage><epage>7345</epage><pages>7339-7345</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)-stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor α chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. 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| subjects | Animals Blotting, Northern CD25 antigen Cell Membrane - metabolism Cell Separation Chromatin - metabolism CREB-Binding Protein DNA-Binding Proteins - metabolism DNA-Binding Proteins - physiology Flow Cytometry Histones - metabolism Interleukin-12 - metabolism Mice Mice, Inbred BALB C Models, Biological Nuclear Proteins - metabolism Polymerase Chain Reaction Precipitin Tests Promoter Regions, Genetic Protein Binding Receptors, Interleukin-2 - biosynthesis Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Spleen - cytology STAT4 protein STAT4 Transcription Factor Time Factors Trans-Activators - metabolism Trans-Activators - physiology Transcription, Genetic |
| title | STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus |
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