Functional Significance of an Overlapping Consensus Binding Motif for Sp1 and Zif268 in the Murine Adenosine Deaminase Gene Promoter
The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissuespecific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-09, Vol.88 (17), p.7523-7527 |
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creator | ACKERMAN, S. L MINDEN, A. G WILLIAMS, G. T BOBONIS, C CHO-YAU YEUNG |
description | The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissuespecific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serumresponsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif. |
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L ; MINDEN, A. G ; WILLIAMS, G. T ; BOBONIS, C ; CHO-YAU YEUNG</creator><creatorcontrib>ACKERMAN, S. L ; MINDEN, A. G ; WILLIAMS, G. T ; BOBONIS, C ; CHO-YAU YEUNG</creatorcontrib><description>The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissuespecific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serumresponsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.17.7523</identifier><identifier>PMID: 1881892</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>3T3 cells ; Adenosine Deaminase - genetics ; Animals ; Antiserum ; Base Sequence ; Binding Sites ; Biological and medical sciences ; Cell growth ; Chromosome Deletion ; Deoxyribonuclease I ; DNA ; DNA-Binding Proteins - metabolism ; Early Growth Response Protein 1 ; Fundamental and applied biological sciences. Psychology ; Gels ; Genes ; Immediate-Early Proteins ; Immunoprecipitation ; Mice ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Mutagenesis, Insertional ; Oligonucleotide Probes ; Promoter regions ; Promoter Regions, Genetic ; Transcription Factors - metabolism ; Transcription, Genetic ; Transcription. Transcription factor. Splicing. Rna processing</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-09, Vol.88 (17), p.7523-7527</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-4587872e321162ea1e523986de100a973c8d450fba29f171a32cf28d15d72aaf3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/17.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2357723$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2357723$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,725,778,782,801,883,27911,27912,53778,53780,58004,58237</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5042759$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1881892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ACKERMAN, S. L</creatorcontrib><creatorcontrib>MINDEN, A. G</creatorcontrib><creatorcontrib>WILLIAMS, G. T</creatorcontrib><creatorcontrib>BOBONIS, C</creatorcontrib><creatorcontrib>CHO-YAU YEUNG</creatorcontrib><title>Functional Significance of an Overlapping Consensus Binding Motif for Sp1 and Zif268 in the Murine Adenosine Deaminase Gene Promoter</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissuespecific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serumresponsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif.</description><subject>3T3 cells</subject><subject>Adenosine Deaminase - genetics</subject><subject>Animals</subject><subject>Antiserum</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cell growth</subject><subject>Chromosome Deletion</subject><subject>Deoxyribonuclease I</subject><subject>DNA</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Early Growth Response Protein 1</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gels</subject><subject>Genes</subject><subject>Immediate-Early Proteins</subject><subject>Immunoprecipitation</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Insertional</subject><subject>Oligonucleotide Probes</subject><subject>Promoter regions</subject><subject>Promoter Regions, Genetic</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcription. Transcription factor. Splicing. 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T</creator><creator>BOBONIS, C</creator><creator>CHO-YAU YEUNG</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19910901</creationdate><title>Functional Significance of an Overlapping Consensus Binding Motif for Sp1 and Zif268 in the Murine Adenosine Deaminase Gene Promoter</title><author>ACKERMAN, S. L ; MINDEN, A. G ; WILLIAMS, G. T ; BOBONIS, C ; CHO-YAU YEUNG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-4587872e321162ea1e523986de100a973c8d450fba29f171a32cf28d15d72aaf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>3T3 cells</topic><topic>Adenosine Deaminase - genetics</topic><topic>Animals</topic><topic>Antiserum</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cell growth</topic><topic>Chromosome Deletion</topic><topic>Deoxyribonuclease I</topic><topic>DNA</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Early Growth Response Protein 1</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gels</topic><topic>Genes</topic><topic>Immediate-Early Proteins</topic><topic>Immunoprecipitation</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Insertional</topic><topic>Oligonucleotide Probes</topic><topic>Promoter regions</topic><topic>Promoter Regions, Genetic</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcription. Transcription factor. Splicing. Rna processing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ACKERMAN, S. L</creatorcontrib><creatorcontrib>MINDEN, A. G</creatorcontrib><creatorcontrib>WILLIAMS, G. 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T</au><au>BOBONIS, C</au><au>CHO-YAU YEUNG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional Significance of an Overlapping Consensus Binding Motif for Sp1 and Zif268 in the Murine Adenosine Deaminase Gene Promoter</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-09-01</date><risdate>1991</risdate><volume>88</volume><issue>17</issue><spage>7523</spage><epage>7527</epage><pages>7523-7527</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissuespecific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serumresponsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1881892</pmid><doi>10.1073/pnas.88.17.7523</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 3T3 cells Adenosine Deaminase - genetics Animals Antiserum Base Sequence Binding Sites Biological and medical sciences Cell growth Chromosome Deletion Deoxyribonuclease I DNA DNA-Binding Proteins - metabolism Early Growth Response Protein 1 Fundamental and applied biological sciences. Psychology Gels Genes Immediate-Early Proteins Immunoprecipitation Mice Molecular and cellular biology Molecular genetics Molecular Sequence Data Mutagenesis, Insertional Oligonucleotide Probes Promoter regions Promoter Regions, Genetic Transcription Factors - metabolism Transcription, Genetic Transcription. Transcription factor. Splicing. Rna processing |
title | Functional Significance of an Overlapping Consensus Binding Motif for Sp1 and Zif268 in the Murine Adenosine Deaminase Gene Promoter |
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