Integrated analysis of molecular and systems level function of the Crp regulon [RNA-Seq]

A fundamental goal of biological research is to connect molecular events with macroscopic physiological phenomena. By incorporating a multi-scale approach that accounts for mechanistic properties of promoters and maps those findings to a genome-scale metabolic-regulatory network, the Escherichia coli Crp regulon is revealed, enabling systems analytics to be applied to delineate its governing role in regulating cellular carbon flow. Genome-wide promoter functions were characterized using ChIP-exo elucidating stable intermediates formed during transcription initiation and distinctions between transcriptional activators and repressors. Genome-wide analysis of Crp regulated genes showed a coordinate regulation of catabolism, anabolism, and energy-generating chemiosmotic processes. Examination of the functional state of the reconstructed regulon during growth on multiple substrates revealed a coherent quantitative adjustment of these overall metabolic processes based on substrate quality, revealing the detailed mechanistic basis for the phenomenologically observed homoeostatic response. Thus, a multi-scale relationship from individual molecular mechanisms to physiological properties is established. RNA-Seq