Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor
Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer...
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Veröffentlicht in: | The Journal of biological chemistry 1999-09, Vol.274 (38), p.26661-26667 |
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creator | Ye, Jianping Young, Howard A. Zhang, Xiaoying Castranova, Vince Vallyathan, Val Shi, Xianglin |
description | Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. YY1 activity is supported by data from mutation and cotransfection analyses. Complexes C and D are formed by nonspecific binding proteins and do not express any regulatory activity in the NIP element. These data indicate that a cell type-specific silencer activity might be determined by a unique profile of ubiquitous transcription factors. |
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In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. YY1 activity is supported by data from mutation and cotransfection analyses. Complexes C and D are formed by nonspecific binding proteins and do not express any regulatory activity in the NIP element. These data indicate that a cell type-specific silencer activity might be determined by a unique profile of ubiquitous transcription factors.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.274.38.26661</identifier><identifier>PMID: 10480868</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AP2 sequence-recognizing factor ; DNA-Binding Proteins - metabolism ; Electrophoresis, Polyacrylamide Gel ; Erythroid-Specific DNA-Binding Factors ; Gene Expression Regulation ; Humans ; Interleukin-3 - genetics ; Jurkat Cells ; nuclear inhibitory protein ; Promoter Regions, Genetic ; Repressor Proteins - genetics ; Transcription Factor AP-2 ; transcription factor YY1 ; Transcription Factors - metabolism ; YY1 protein ; YY1 Transcription Factor</subject><ispartof>The Journal of biological chemistry, 1999-09, Vol.274 (38), p.26661-26667</ispartof><rights>1999 © 1999 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-38b1d8302d2958593e24a835878b32fa74a010ffec2a0fefcac31978c709aa33</citedby><cites>FETCH-LOGICAL-c448t-38b1d8302d2958593e24a835878b32fa74a010ffec2a0fefcac31978c709aa33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10480868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Jianping</creatorcontrib><creatorcontrib>Young, Howard A.</creatorcontrib><creatorcontrib>Zhang, Xiaoying</creatorcontrib><creatorcontrib>Castranova, Vince</creatorcontrib><creatorcontrib>Vallyathan, Val</creatorcontrib><creatorcontrib>Shi, Xianglin</creatorcontrib><title>Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. YY1 activity is supported by data from mutation and cotransfection analyses. Complexes C and D are formed by nonspecific binding proteins and do not express any regulatory activity in the NIP element. These data indicate that a cell type-specific silencer activity might be determined by a unique profile of ubiquitous transcription factors.</description><subject>AP2 sequence-recognizing factor</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Erythroid-Specific DNA-Binding Factors</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Interleukin-3 - genetics</subject><subject>Jurkat Cells</subject><subject>nuclear inhibitory protein</subject><subject>Promoter Regions, Genetic</subject><subject>Repressor Proteins - genetics</subject><subject>Transcription Factor AP-2</subject><subject>transcription factor YY1</subject><subject>Transcription Factors - metabolism</subject><subject>YY1 protein</subject><subject>YY1 Transcription Factor</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtr3DAUhUVoSaZp9l0VLUp3nuphj-XswtA8INDQzCJZCVm-mlFiS45kt0z_Sv9sNeNZlEDpBXFBfOdwOQehD5TMKSnzL0-1nrMyn3MxZ4vFgh6hGSWCZ7ygD2_QjBBGs4oV4gS9i_GJpMkreoxOKMkFEQsxQ7-_w3ps1WC9w95ghZfQtni17SGLPWhrrMb3tgWnIWDr8LABfD12yuEbN0BoYXy2LuP4Chzgu-A7n35xvd2Dq6Bc1MH2e_tLpQcf8OMjxco16eGLO4bv4WXcuWcBtF87-8u69QF9j94a1UY4O-xTtLr8ulpeZ7ffrm6WF7eZznMxZFzUtBGcsIZVhSgqDixXgheiFDVnRpW5IpQYA5opYsBopTmtSqFLUinF-Sn6PNn2wadb4iA7G3WKQTnwY5RlirHinP4XpCWvaMGLBJIJ1MHHGMDIPthOha2kRO6Kk6k4mYqTXMh9cUny8eA91h00fwmmphLwaQI2dr35aQPI2nq9ge61z_mEQQrsh4Ugo7a7fJsk0YNsvP33EX8AzxG0CQ</recordid><startdate>19990917</startdate><enddate>19990917</enddate><creator>Ye, Jianping</creator><creator>Young, Howard A.</creator><creator>Zhang, Xiaoying</creator><creator>Castranova, Vince</creator><creator>Vallyathan, Val</creator><creator>Shi, Xianglin</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>19990917</creationdate><title>Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor</title><author>Ye, Jianping ; Young, Howard A. ; Zhang, Xiaoying ; Castranova, Vince ; Vallyathan, Val ; Shi, Xianglin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-38b1d8302d2958593e24a835878b32fa74a010ffec2a0fefcac31978c709aa33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>AP2 sequence-recognizing factor</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Erythroid-Specific DNA-Binding Factors</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Interleukin-3 - genetics</topic><topic>Jurkat Cells</topic><topic>nuclear inhibitory protein</topic><topic>Promoter Regions, Genetic</topic><topic>Repressor Proteins - genetics</topic><topic>Transcription Factor AP-2</topic><topic>transcription factor YY1</topic><topic>Transcription Factors - metabolism</topic><topic>YY1 protein</topic><topic>YY1 Transcription Factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ye, Jianping</creatorcontrib><creatorcontrib>Young, Howard A.</creatorcontrib><creatorcontrib>Zhang, Xiaoying</creatorcontrib><creatorcontrib>Castranova, Vince</creatorcontrib><creatorcontrib>Vallyathan, Val</creatorcontrib><creatorcontrib>Shi, Xianglin</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>Ye, Jianping</au><au>Young, Howard A.</au><au>Zhang, Xiaoying</au><au>Castranova, Vince</au><au>Vallyathan, Val</au><au>Shi, Xianglin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1999-09-17</date><risdate>1999</risdate><volume>274</volume><issue>38</issue><spage>26661</spage><epage>26667</epage><pages>26661-26667</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. YY1 activity is supported by data from mutation and cotransfection analyses. Complexes C and D are formed by nonspecific binding proteins and do not express any regulatory activity in the NIP element. These data indicate that a cell type-specific silencer activity might be determined by a unique profile of ubiquitous transcription factors.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10480868</pmid><doi>10.1074/jbc.274.38.26661</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | AP2 sequence-recognizing factor DNA-Binding Proteins - metabolism Electrophoresis, Polyacrylamide Gel Erythroid-Specific DNA-Binding Factors Gene Expression Regulation Humans Interleukin-3 - genetics Jurkat Cells nuclear inhibitory protein Promoter Regions, Genetic Repressor Proteins - genetics Transcription Factor AP-2 transcription factor YY1 Transcription Factors - metabolism YY1 protein YY1 Transcription Factor |
title | Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor |
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