The complexities of gene regulation in E. coli

We are currently identifying genes that belong to the Sxy regulon in E. coli. The only other well-characterized Sxy regulon was identified by our work in H. influenzae (link). E. coli’s genome is over 2-times larger than H. influenzae’s and, not surprisingly, the E. coli Sxy regulon contains more genes. The E. coli regulon has an additional level of complexity because many of the Sxy-regulated genes are likely to have additional protein regulators (ie. Sxy-regulated genes also belong to other regulons).

This additional complexity is a consequence of lifestyle. E. coli is a more versatile organism than H. influenzae: it can make most of its organic molecules from scratch (aka. from simple sugars plus a few inorganic nutrients) and it can survive in various different environments.

Because a bacterium must at all times satisfy multiple metabolic requirements, it needs to continuously balance its internal functions while exploiting a potentially ever-changing external environment. Bacteria that inhabit very stable niches (such as H. influenzae, which lives in the cavities of a human host) have a small number of transcription factors, whereas bacteria in more complex environments employ a much larger number of regulators. This relationship has been shown to scale as a power-law in which the number of transcription factors doubles twice as fast as does the total number of genes in a genome (van Nimwegen,E., 2003, Trends Genet., 19, 479), indicating that large bacterial genomes employ disproportionately more complex regulatory networks.

Thus, E. coli’s lifestyle necessitates more sensory and response systems than does that of H. influenzae. Consequently, the genes in E. coli’s Sxy regulon are much more likely to belong to multiple (possibly non-overlapping) regulatory networks in order to fine-tune their expression. This unfortunately makes studying the E. coli Sxy regulon more complicated; we can’t be confident that overexpression of the Sxy protein results in induction of all Sxy-regulated genes.

For H. influenzae, gene expression data coupled with bioinformatic analysis revealed that most genes in the Sxy regulon require only CRP and Sxy for transcription activation in standard culture conditions. In E. coli, some Sxy regulon genes will likely be repressed during growth in standard culture conditions, regardless of whether CRP and Sxy are trying to turn them on. Perhaps conducting E. coli gene induction studies in minimal medium will reduce the activities of repressor proteins and so improve our ability to detect some members of the Sxy regulon.

Fortunately, a substantial body of knowledge surrounds the regulation of some of the genes in E. coli’s Sxy regulon. Thus, although we will have trouble identifying genes that can’t be induced by Sxy in standard lab conditions, we will at least be able to integrate our Sxy regulon data with other regulatory networks.