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Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops

Feed-forward loops (FFLs) represent an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concen...

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Autores principales: Yang, Chi-Dung, Huang, Hsi-Yuan, Shrestha, Sirjana, Chen, Yen-Hua, Huang, Hsien-Da, Tseng, Ching-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121374/
https://www.ncbi.nlm.nih.gov/pubmed/30096859
http://dx.doi.org/10.3390/ijms19082335
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author Yang, Chi-Dung
Huang, Hsi-Yuan
Shrestha, Sirjana
Chen, Yen-Hua
Huang, Hsien-Da
Tseng, Ching-Ping
author_facet Yang, Chi-Dung
Huang, Hsi-Yuan
Shrestha, Sirjana
Chen, Yen-Hua
Huang, Hsien-Da
Tseng, Ching-Ping
author_sort Yang, Chi-Dung
collection PubMed
description Feed-forward loops (FFLs) represent an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs, such as araBAD and araFGH operons and adapts to fluctuating environmental nutrients, thereby enhancing the survivability of E. coli. Although computational simulations have been conducted to explore the potential functionality of FFLs, a comprehensive study on the functions of all structural types on the basis of in vivo data is lacking. Moreover, the regulatory role of CRP-mediated FFLs (CRP-FFLs) remains obscure. We identified 393 CRP-FFLs in E. coli using EcoCyc and RegulonDB. Dose–response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, which were further divided into five functional groups. The microarray and reported regulatory relationships identified 202 CRP-FFLs that were directly regulated by CRP in these eight types of FFLs. Interestingly, 34% (147/432) of genes were directly regulated by CRP and CRP-regulated TFs, which indicates that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.
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spelling pubmed-61213742018-09-07 Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops Yang, Chi-Dung Huang, Hsi-Yuan Shrestha, Sirjana Chen, Yen-Hua Huang, Hsien-Da Tseng, Ching-Ping Int J Mol Sci Article Feed-forward loops (FFLs) represent an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs, such as araBAD and araFGH operons and adapts to fluctuating environmental nutrients, thereby enhancing the survivability of E. coli. Although computational simulations have been conducted to explore the potential functionality of FFLs, a comprehensive study on the functions of all structural types on the basis of in vivo data is lacking. Moreover, the regulatory role of CRP-mediated FFLs (CRP-FFLs) remains obscure. We identified 393 CRP-FFLs in E. coli using EcoCyc and RegulonDB. Dose–response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, which were further divided into five functional groups. The microarray and reported regulatory relationships identified 202 CRP-FFLs that were directly regulated by CRP in these eight types of FFLs. Interestingly, 34% (147/432) of genes were directly regulated by CRP and CRP-regulated TFs, which indicates that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs. MDPI 2018-08-09 /pmc/articles/PMC6121374/ /pubmed/30096859 http://dx.doi.org/10.3390/ijms19082335 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Chi-Dung
Huang, Hsi-Yuan
Shrestha, Sirjana
Chen, Yen-Hua
Huang, Hsien-Da
Tseng, Ching-Ping
Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title_full Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title_fullStr Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title_full_unstemmed Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title_short Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops
title_sort large-scale functional analysis of crp-mediated feed-forward loops
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121374/
https://www.ncbi.nlm.nih.gov/pubmed/30096859
http://dx.doi.org/10.3390/ijms19082335
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