Abstract
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.
Highlights
Microbes must accustom to environmental changes produced by physiological signals, such as nutrients, salts and molecular species and physicochemical states, such as temperature, redox potential and osmolality to survive [1]
CRP-Feed-forward loops (FFLs) consisting of 292 genes and 43 transcription factor (TF)
To obtain and clarify the functional CRP-FFLs in E. coli, cAMP dose–response experiments were performed by microarray as follows
Summary
Microbes must accustom to environmental changes produced by physiological signals, such as nutrients, salts and molecular species and physicochemical states, such as temperature, redox potential and osmolality to survive [1]. Escherichia coli regulates gene expressions using considerable different gene regulators, such as transcription factors (TFs), to react to those environmental signals [2]. Databases such as EcoCyc 22.0 [3] and RegulonDB 9.4 [4,5] have reported 201 TFs in E. coli. A complicated gene regulation network (GRN) is formed by linking the regulation information between.
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