Nutrient Regulation of Gene Expression

The majority of bacterial promoters are regulated by at least two transcription factors. Many of these promoters are regulated by two activators, with expression being co-dependent on the activity of both activators [l] . At most of these promoters, one of the activators responds to a ‘global’ regulatory signal whilst the other responds to a ‘specific’ signal. For example, transcription initiation at the Escherichia coli nu& promoter is induced by oxygen starvation (a global signal, interpreted by the global regulator, FNR) and nitrate ions (a specific metabolic signal, interpreted by NarL). The E. coli nu& promoter is co-dependent on FNR and NarL. We are interested in understanding the mechanisms by which expression from a promoter can be codependent on two activators. In recent studies with promoters regulated by single transcription activators, we have demonstrated that direct protein-protein interaction between the activator and RNA polymerase (NAP) is essential for transcription activation. A number of studies have shown that RNAP carries two separate contact sites for such activators: one is located in the C-terminal domain of the a-subunit (aCTD) whilst the other is near the C-terminus of the a-subunit (reviewed in [2,3]). Most activators that make contact with a bind just upstream of the -35 region, whilst activators that contact aCTD generally bind further upstream. This suggests a simple model to explain co-dependence on two activators, illustrated in Figure 1, in which one of