Identifying global regulators in transcriptional regulatory networks in bacteria

Abstract

The machinery for cells to take decisions, when environmental conditions change, includes protein-DNA interactions defined by transcriptional factors and their targets around promoters. Properties of global regulators are revised attempting to reach diagnostic explicit criteria for their definition and eventual future computational identification. These include among others, the number of regulated genes, the number and type of co-regulators, the different sigma-classes of promoters and the number of transcriptional factors they regulate, the size of the evolutionary family they belong to, and the variety of conditions where they exert their control. As a consequence, global versus local regulation can be identified, as shown for Escherichia coli and eventually in other genomes.

A Hybrid of Metabolic Flux Analysis and Bayesian Factor Modeling for Multiomic Temporal Pathway Activation

“…As expected, the nucleotide salvage pathway (PID:5) highly responds to the environment where oxygen was present, while valine, leucine, and isoleucine metabolism pathway (PID:17) and alanine and which is designated as a global transcription factor in E. coli (32 ). A recent experiment confirmed that the activity of Lrp decreases as aerobiosis increases (33 ).…”

Transcription factor binding kinetics constrain noise suppression via negative feedback

“…In E. coli, the expression of 51% of all genes are under control of seven highly expressed global transcriptional regulators (CRP, FNR, IHF, FIS, ArcA, NarL and Lrp). Among these all but ArcA are employing negative feedback on their own synthesis 6,7 . However, all the six TFs bind weakly to the operators mediating the feedback compared with their binding to other specific sites (Fig.…”

“…Negative feedback is therefore commonly used to maintain homeostasis and to reduce the fluctuations in intracellular processes such as gene expression [3][4][5] . For example, nearly half of the B300 transcription factors (TFs) in Escherichia coli make use of negative feedback on their own expression 6,7 . However, the chemical noise that makes regulation necessary also limits the accuracy of feedback regulation 8 .…”

Structure and evolution of gene regulatory networks in microbial genomes

“…Global transcription regulators have been defined as those TFs that have the ability to: regulate large number of genes belonging to diverse functional classes, control a complex regulatory cascade by both directly and indirectly effect expression of various cellular pathways and act on target promoters that use different sigma factors [46]. Based on this, seven global regulators in E. coli have been proposed, which control more than 50% of the genes in the entire transcriptional regulatory network.…”