The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally.
Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by m...
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| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003839&type=printable |
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| author | Dan M Park Md Sohail Akhtar Aseem Z Ansari Robert Landick Patricia J Kiley |
| author_facet | Dan M Park Md Sohail Akhtar Aseem Z Ansari Robert Landick Patricia J Kiley |
| author_sort | Dan M Park |
| collection | DOAJ |
| description | Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ(70)-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis. |
| format | Article |
| id | doaj-art-a0cb9c0de9b54cb39901c22118d0ea65 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-a0cb9c0de9b54cb39901c22118d0ea652025-01-16T05:31:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-01910e100383910.1371/journal.pgen.1003839The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally.Dan M ParkMd Sohail AkhtarAseem Z AnsariRobert LandickPatricia J KileyDespite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ(70)-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003839&type=printable |
| spellingShingle | Dan M Park Md Sohail Akhtar Aseem Z Ansari Robert Landick Patricia J Kiley The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. PLoS Genetics |
| title | The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. |
| title_full | The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. |
| title_fullStr | The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. |
| title_full_unstemmed | The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. |
| title_short | The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. |
| title_sort | bacterial response regulator arca uses a diverse binding site architecture to regulate carbon oxidation globally |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003839&type=printable |
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