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Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators

TetR family transcriptional regulators (TFRs) are found in most bacteria and archea. Most of the family members that have been investigated to date are repressors of their target genes, and the majority of these, like the well-characterized protein TetR, regulate genes that encode transmembrane effl...

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Autores principales: Ahn, Sang Kyun, Cuthbertson, Leslie, Nodwell, Justin R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511530/
https://www.ncbi.nlm.nih.gov/pubmed/23226315
http://dx.doi.org/10.1371/journal.pone.0050562
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author Ahn, Sang Kyun
Cuthbertson, Leslie
Nodwell, Justin R.
author_facet Ahn, Sang Kyun
Cuthbertson, Leslie
Nodwell, Justin R.
author_sort Ahn, Sang Kyun
collection PubMed
description TetR family transcriptional regulators (TFRs) are found in most bacteria and archea. Most of the family members that have been investigated to date are repressors of their target genes, and the majority of these, like the well-characterized protein TetR, regulate genes that encode transmembrane efflux pumps. In many cases repression by TFR proteins is reversed through the direct binding of a small-molecule ligand. The number of TFRs in the public database has grown rapidly as a result of genome sequencing and there are now thousands of family members; however virtually nothing is known about the biology and biochemistry they regulate. Generally applicable methods for predicting their regulatory targets would assist efforts to characterize the family. Here, we investigate chromosomal context of 372 TFRs from three Streptomyces species. We find that the majority (250 TFRs) are transcribed divergently from one neighboring gene, as is the case for TetR and its target tetA. We explore predicted target gene product identity and intergenic separation to see which either correlates with a direct regulatory relationship. While intergenic separation is a critical factor in regulatory prediction the identity of the putative target gene product is not. Our data suggest that those TFRs that are <200 bp from their divergently oriented neighbors are most likely to regulate them. These target genes include membrane proteins (26% of which 22% are probable membrane-associated pumps), enzymes (60%), other proteins such as transcriptional regulators (1%), and proteins having no predictive sequence motifs (13%). In addition to establishing a solid foundation for identifying targets for TFRs of unknown function, our analysis demonstrates a much greater diversity of TFR-regulated biochemical functions.
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spelling pubmed-35115302012-12-05 Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators Ahn, Sang Kyun Cuthbertson, Leslie Nodwell, Justin R. PLoS One Research Article TetR family transcriptional regulators (TFRs) are found in most bacteria and archea. Most of the family members that have been investigated to date are repressors of their target genes, and the majority of these, like the well-characterized protein TetR, regulate genes that encode transmembrane efflux pumps. In many cases repression by TFR proteins is reversed through the direct binding of a small-molecule ligand. The number of TFRs in the public database has grown rapidly as a result of genome sequencing and there are now thousands of family members; however virtually nothing is known about the biology and biochemistry they regulate. Generally applicable methods for predicting their regulatory targets would assist efforts to characterize the family. Here, we investigate chromosomal context of 372 TFRs from three Streptomyces species. We find that the majority (250 TFRs) are transcribed divergently from one neighboring gene, as is the case for TetR and its target tetA. We explore predicted target gene product identity and intergenic separation to see which either correlates with a direct regulatory relationship. While intergenic separation is a critical factor in regulatory prediction the identity of the putative target gene product is not. Our data suggest that those TFRs that are <200 bp from their divergently oriented neighbors are most likely to regulate them. These target genes include membrane proteins (26% of which 22% are probable membrane-associated pumps), enzymes (60%), other proteins such as transcriptional regulators (1%), and proteins having no predictive sequence motifs (13%). In addition to establishing a solid foundation for identifying targets for TFRs of unknown function, our analysis demonstrates a much greater diversity of TFR-regulated biochemical functions. Public Library of Science 2012-11-30 /pmc/articles/PMC3511530/ /pubmed/23226315 http://dx.doi.org/10.1371/journal.pone.0050562 Text en © 2012 Ahn et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ahn, Sang Kyun
Cuthbertson, Leslie
Nodwell, Justin R.
Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title_full Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title_fullStr Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title_full_unstemmed Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title_short Genome Context as a Predictive Tool for Identifying Regulatory Targets of the TetR Family Transcriptional Regulators
title_sort genome context as a predictive tool for identifying regulatory targets of the tetr family transcriptional regulators
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511530/
https://www.ncbi.nlm.nih.gov/pubmed/23226315
http://dx.doi.org/10.1371/journal.pone.0050562
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