Modeling feedback loops in the H-NS-mediated regulation of the Escherichia coli bgl operon

Abstract

The histone-like nucleoid-associated protein H-NS is a global transcriptional repressor that controls approximately 5% of all genes in Escherichia coli and other enterobacteria. H-NS binds to DNA with low specificity. Nonetheless, repression of some loci is exceptionally specific. Experimental data for the E. coli bgl operon suggest that highly specific repression is caused by regulatory feedback loops. To analyze whether such feedback loops can account for the observed specificity of repression, here a model was built based on expression data. The model includes several regulatory interactions, which are synergy of repression by binding of H-NS to two regulatory elements, an inverse correlation of the rate of repression by H-NS and transcription, and a threshold for positive regulation by anti-terminator BglG, which is encoded within the operon. The latter two regulatory interactions represent feedback loops in the model. The resulting system of equations was solved for the expression level of the operon and analyzed with respect to different promoter activities. This analysis demonstrates that a small (3-fold) increase of the bgl promoter activity results in a strong (80-fold) enhancement of bgl operon expression. Thus, the parameters included into the model are sufficient to simulate specific repression by H-NS.