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Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655

Transcriptional regulation enables cells to respond to environmental changes. Of the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, 185 have been experimentally identified, but ChIP methods have been used to fully characterize only a few dozen. Identifying these...

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Autores principales: Gao, Ye, Yurkovich, James T, Seo, Sang Woo, Kabimoldayev, Ilyas, Dräger, Andreas, Chen, Ke, Sastry, Anand V, Fang, Xin, Mih, Nathan, Yang, Laurence, Eichner, Johannes, Cho, Byung-Kwan, Kim, Donghyuk, Palsson, Bernhard O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237786/
https://www.ncbi.nlm.nih.gov/pubmed/30137486
http://dx.doi.org/10.1093/nar/gky752
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author Gao, Ye
Yurkovich, James T
Seo, Sang Woo
Kabimoldayev, Ilyas
Dräger, Andreas
Chen, Ke
Sastry, Anand V
Fang, Xin
Mih, Nathan
Yang, Laurence
Eichner, Johannes
Cho, Byung-Kwan
Kim, Donghyuk
Palsson, Bernhard O
author_facet Gao, Ye
Yurkovich, James T
Seo, Sang Woo
Kabimoldayev, Ilyas
Dräger, Andreas
Chen, Ke
Sastry, Anand V
Fang, Xin
Mih, Nathan
Yang, Laurence
Eichner, Johannes
Cho, Byung-Kwan
Kim, Donghyuk
Palsson, Bernhard O
author_sort Gao, Ye
collection PubMed
description Transcriptional regulation enables cells to respond to environmental changes. Of the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, 185 have been experimentally identified, but ChIP methods have been used to fully characterize only a few dozen. Identifying these remaining TFs is key to improving our knowledge of the E. coli transcriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to (i) identify 16 candidate TFs from over a hundred uncharacterized genes; (ii) capture a total of 255 DNA binding peaks for ten candidate TFs resulting in six high-confidence binding motifs; (iii) reconstruct the regulons of these ten TFs by determining gene expression changes upon deletion of each TF and (iv) identify the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of l-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron-limited conditions, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel.
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spelling pubmed-62377862018-11-21 Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655 Gao, Ye Yurkovich, James T Seo, Sang Woo Kabimoldayev, Ilyas Dräger, Andreas Chen, Ke Sastry, Anand V Fang, Xin Mih, Nathan Yang, Laurence Eichner, Johannes Cho, Byung-Kwan Kim, Donghyuk Palsson, Bernhard O Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Transcriptional regulation enables cells to respond to environmental changes. Of the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, 185 have been experimentally identified, but ChIP methods have been used to fully characterize only a few dozen. Identifying these remaining TFs is key to improving our knowledge of the E. coli transcriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to (i) identify 16 candidate TFs from over a hundred uncharacterized genes; (ii) capture a total of 255 DNA binding peaks for ten candidate TFs resulting in six high-confidence binding motifs; (iii) reconstruct the regulons of these ten TFs by determining gene expression changes upon deletion of each TF and (iv) identify the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of l-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron-limited conditions, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel. Oxford University Press 2018-11-16 2018-08-23 /pmc/articles/PMC6237786/ /pubmed/30137486 http://dx.doi.org/10.1093/nar/gky752 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Gao, Ye
Yurkovich, James T
Seo, Sang Woo
Kabimoldayev, Ilyas
Dräger, Andreas
Chen, Ke
Sastry, Anand V
Fang, Xin
Mih, Nathan
Yang, Laurence
Eichner, Johannes
Cho, Byung-Kwan
Kim, Donghyuk
Palsson, Bernhard O
Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title_full Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title_fullStr Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title_full_unstemmed Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title_short Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655
title_sort systematic discovery of uncharacterized transcription factors in escherichia coli k-12 mg1655
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237786/
https://www.ncbi.nlm.nih.gov/pubmed/30137486
http://dx.doi.org/10.1093/nar/gky752
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