Combinatorial transcriptional control of the lactose operon of Escherichia coli
The goal of systems biology is to understand the behavior of the whole in terms of knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents involved in a biological system and their complex web of interactions. The lac promoter of Es...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-04, Vol.104 (14), p.6043-6048 |
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| creator | Kuhlman, Thomas Zhang, Zhongge Saier, Milton H. Jr Hwa, Terence |
| description | The goal of systems biology is to understand the behavior of the whole in terms of knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents involved in a biological system and their complex web of interactions. The lac promoter of Escherichia coli offers the possibility of confronting "system-level" properties of transcriptional regulation with the known biochemistry of the molecular constituents and their mutual interactions. Such confrontations can reveal previously unknown constituents and interactions, as well as offer insight into how the components work together as a whole. Here we study the combinatorial control of the lac promoter by the regulators Lac repressor (LacR) and cAMP-receptor protein (CRP). A previous in vivo study [Setty Y, Mayo AE, Surette MG, Alon U (2003) Proc Natl Acad Sci USA 100:7702-7707] found gross disagreement between the observed promoter activities and the expected behavior based on the known molecular mechanisms. We repeated the study by identifying and removing several extraneous factors that significantly modulated the expression of the lac promoter. Through quantitative, systematic characterization of promoter activity for a number of key mutants and guided by the thermodynamic model of transcriptional regulation, we were able to account for the combinatorial control of the lac promoter quantitatively, in terms of a cooperative interaction between CRP and LacR-mediated DNA looping. Specifically, our analysis indicates that the sensitivity of the inducer response results from LacR-mediated DNA looping, which is significantly enhanced by CRP. |
| doi_str_mv | 10.1073/pnas.0606717104 |
| format | Article |
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Jr ; Hwa, Terence</creator><creatorcontrib>Kuhlman, Thomas ; Zhang, Zhongge ; Saier, Milton H. Jr ; Hwa, Terence</creatorcontrib><description>The goal of systems biology is to understand the behavior of the whole in terms of knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents involved in a biological system and their complex web of interactions. The lac promoter of Escherichia coli offers the possibility of confronting "system-level" properties of transcriptional regulation with the known biochemistry of the molecular constituents and their mutual interactions. Such confrontations can reveal previously unknown constituents and interactions, as well as offer insight into how the components work together as a whole. Here we study the combinatorial control of the lac promoter by the regulators Lac repressor (LacR) and cAMP-receptor protein (CRP). A previous in vivo study [Setty Y, Mayo AE, Surette MG, Alon U (2003) Proc Natl Acad Sci USA 100:7702-7707] found gross disagreement between the observed promoter activities and the expected behavior based on the known molecular mechanisms. We repeated the study by identifying and removing several extraneous factors that significantly modulated the expression of the lac promoter. Through quantitative, systematic characterization of promoter activity for a number of key mutants and guided by the thermodynamic model of transcriptional regulation, we were able to account for the combinatorial control of the lac promoter quantitatively, in terms of a cooperative interaction between CRP and LacR-mediated DNA looping. Specifically, our analysis indicates that the sensitivity of the inducer response results from LacR-mediated DNA looping, which is significantly enhanced by CRP.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0606717104</identifier><identifier>PMID: 17376875</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Bacteriology ; Biochemistry ; Biological Sciences ; Cell growth ; Cooperation ; Cyclic AMP Receptor Protein - metabolism ; Data lines ; Deoxyribonucleic acid ; DNA ; DNA, Bacterial - chemistry ; E coli ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - growth & development ; Gene expression ; Gene Expression Regulation, Bacterial ; Genes ; Genes, Bacterial ; Lac Operon ; Mathematical independent variables ; Nucleic Acid Conformation ; Parametric models ; Promoter Regions, Genetic ; Repression ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Sugar ; Systems Biology ; Thermodynamics ; Transcription, Genetic</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-04, Vol.104 (14), p.6043-6048</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Apr 3, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-6a02c5a1382a4ec5c54f390e0ec38a88cdbf71df0987f524def65cde8bf0313b3</citedby><cites>FETCH-LOGICAL-c552t-6a02c5a1382a4ec5c54f390e0ec38a88cdbf71df0987f524def65cde8bf0313b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/14.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25427323$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25427323$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17376875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuhlman, Thomas</creatorcontrib><creatorcontrib>Zhang, Zhongge</creatorcontrib><creatorcontrib>Saier, Milton H. Jr</creatorcontrib><creatorcontrib>Hwa, Terence</creatorcontrib><title>Combinatorial transcriptional control of the lactose operon of Escherichia coli</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The goal of systems biology is to understand the behavior of the whole in terms of knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents involved in a biological system and their complex web of interactions. The lac promoter of Escherichia coli offers the possibility of confronting "system-level" properties of transcriptional regulation with the known biochemistry of the molecular constituents and their mutual interactions. Such confrontations can reveal previously unknown constituents and interactions, as well as offer insight into how the components work together as a whole. Here we study the combinatorial control of the lac promoter by the regulators Lac repressor (LacR) and cAMP-receptor protein (CRP). A previous in vivo study [Setty Y, Mayo AE, Surette MG, Alon U (2003) Proc Natl Acad Sci USA 100:7702-7707] found gross disagreement between the observed promoter activities and the expected behavior based on the known molecular mechanisms. We repeated the study by identifying and removing several extraneous factors that significantly modulated the expression of the lac promoter. Through quantitative, systematic characterization of promoter activity for a number of key mutants and guided by the thermodynamic model of transcriptional regulation, we were able to account for the combinatorial control of the lac promoter quantitatively, in terms of a cooperative interaction between CRP and LacR-mediated DNA looping. Specifically, our analysis indicates that the sensitivity of the inducer response results from LacR-mediated DNA looping, which is significantly enhanced by CRP.</description><subject>Bacteriology</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Cell growth</subject><subject>Cooperation</subject><subject>Cyclic AMP Receptor Protein - metabolism</subject><subject>Data lines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Bacterial - chemistry</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - growth & development</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Genes</subject><subject>Genes, Bacterial</subject><subject>Lac Operon</subject><subject>Mathematical independent variables</subject><subject>Nucleic Acid Conformation</subject><subject>Parametric models</subject><subject>Promoter Regions, Genetic</subject><subject>Repression</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Sugar</subject><subject>Systems Biology</subject><subject>Thermodynamics</subject><subject>Transcription, Genetic</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EokvhzAmIekBc0o6_kwsSWpUPqVIP0LPlOHbXq2y82E4F_74OG3WBA5yssZ95PTPvIPQSwzkGSS_2o07nIEBILDGwR2iFocW1YC08RisAIuuGEXaCnqW0BYCWN_AUnWBJpWgkX6Hrddh1ftQ5RK-HKkc9JhP9PvswltiEMccwVMFVeWOrQZsckq3C3sYwzreXyWxs9GbjdYEH_xw9cXpI9sVynqKbj5ff1p_rq-tPX9YfrmrDOcm10EAM15g2RDNruOHM0RYsWEMb3TSm75zEvYO2kY4T1lsnuOlt0zmgmHb0FL0_6O6nbmd7Y0udelD76Hc6_lRBe_Xny-g36jbcKdxwLDAtAm8XgRi-TzZltfPJ2GHQow1TUhIop4T8H8StEIwSUcCzv8BtmGKZYlIEMMNS0Fnt4gCZGFKK1j2UjEHNlqrZUnW0tGS8_r3TI794WIA3CzBnHuWYwkyJolCId_8mlJuGIdsfuaCvDug2lZV4YAlnRNJf01g-czoofRt9UjdfS3sUQArGCKb3bK3JPQ</recordid><startdate>20070403</startdate><enddate>20070403</enddate><creator>Kuhlman, Thomas</creator><creator>Zhang, Zhongge</creator><creator>Saier, Milton H. 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Jr ; Hwa, Terence</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-6a02c5a1382a4ec5c54f390e0ec38a88cdbf71df0987f524def65cde8bf0313b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Bacteriology</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Cell growth</topic><topic>Cooperation</topic><topic>Cyclic AMP Receptor Protein - metabolism</topic><topic>Data lines</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Bacterial - chemistry</topic><topic>E coli</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - growth & development</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Bacterial</topic><topic>Genes</topic><topic>Genes, Bacterial</topic><topic>Lac Operon</topic><topic>Mathematical independent variables</topic><topic>Nucleic Acid Conformation</topic><topic>Parametric models</topic><topic>Promoter Regions, Genetic</topic><topic>Repression</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Sugar</topic><topic>Systems Biology</topic><topic>Thermodynamics</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuhlman, Thomas</creatorcontrib><creatorcontrib>Zhang, Zhongge</creatorcontrib><creatorcontrib>Saier, Milton H. 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Jr</au><au>Hwa, Terence</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combinatorial transcriptional control of the lactose operon of Escherichia coli</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2007-04-03</date><risdate>2007</risdate><volume>104</volume><issue>14</issue><spage>6043</spage><epage>6048</epage><pages>6043-6048</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The goal of systems biology is to understand the behavior of the whole in terms of knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents involved in a biological system and their complex web of interactions. 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Through quantitative, systematic characterization of promoter activity for a number of key mutants and guided by the thermodynamic model of transcriptional regulation, we were able to account for the combinatorial control of the lac promoter quantitatively, in terms of a cooperative interaction between CRP and LacR-mediated DNA looping. Specifically, our analysis indicates that the sensitivity of the inducer response results from LacR-mediated DNA looping, which is significantly enhanced by CRP.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17376875</pmid><doi>10.1073/pnas.0606717104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Bacteriology Biochemistry Biological Sciences Cell growth Cooperation Cyclic AMP Receptor Protein - metabolism Data lines Deoxyribonucleic acid DNA DNA, Bacterial - chemistry E coli Escherichia coli Escherichia coli - genetics Escherichia coli - growth & development Gene expression Gene Expression Regulation, Bacterial Genes Genes, Bacterial Lac Operon Mathematical independent variables Nucleic Acid Conformation Parametric models Promoter Regions, Genetic Repression Repressor Proteins - genetics Repressor Proteins - metabolism Sugar Systems Biology Thermodynamics Transcription, Genetic |
| title | Combinatorial transcriptional control of the lactose operon of Escherichia coli |
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