Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 6 June 2018 / Approved: 6 June 2018 / Online: 6 June 2018 (16:00:56 CEST)

A peer-reviewed article of this Preprint also exists.

Yang, C.-D.; Huang, H.-Y.; Shrestha, S.; Chen, Y.-H.; Huang, H.-D.; Tseng, C.-P. Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops. Int. J. Mol. Sci. 2018, 19, 2335. Yang, C.-D.; Huang, H.-Y.; Shrestha, S.; Chen, Y.-H.; Huang, H.-D.; Tseng, C.-P. Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops. Int. J. Mol. Sci. 2018, 19, 2335.

Journal reference: Int. J. Mol. Sci. 2018, 19, 2335
DOI: 10.3390/ijms19082335

Abstract

The feed-forward loop (FFL) is 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 like araBAD and araFGH operons and adapt to fluctuating environmental nutrients thus enhancing the survivability of E. coli. Although computational simulations have been used to explore the potential functionality of FFLs, a comprehensive study of the functions of all structural types based on in vivo data is lacking. Also, the regulatory role of CRP-mediated feed-forward loops (CRP-FFLs) remain unclear to date. Using EcoCyc and RegulonDB, we identified 393 CRP-FFLs in the E. coli. 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, that were further divided into five functional groups. Microarray and reported regulatory relationships identified 202 CRP-FFLs which were directly regulated by CRP in these eight types of FFLs. Interestingly, 30% (147/482) of genes were directly regulated by CRP and CRP-regulated TFs, indicating 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.

Subject Areas

feed-forward loop (FFL); cAMP receptor protein (CRP); transcriptional factor (TF).

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