Long-range Cooperativity Between Gene Regulatory Sequences in a Prokaryote

Regulation of transcription initiation by proteins binding at DNA sequences some distance from the promoter region itself seems to be a general phenomenon in both eukaryotes and prokaryotes. Proteins bound to an enhancer site in eukaryotes can turn on a distant gene, whereas efficient repression of some prokaryotic genes such as the gal, ara and deo operons of Escherichia coli, requires the presence of two operator sites, separated by 110, 200 and 600 base pairs (bp) respectively. In the deo operon, which encodes nucleoside catabolizing enzymes, we have shown that efficient and cooperative repression can be obtained when the distance between the two sites ranges from 224 to 997 bp. Here, we report that transcription initiation can be regulated from an operator site placed 1 to 5 kilobases (kb) downstream of the deoP2 promoter (and downstream of the transcribed gene), and present the first experimental data for prokaryotic regulation at distances greater than 1 kb. Our results support the model of DNA loop formation as a common regulatory mechanism explaining both some prokaryotic regulation and the action of eukaryotic enhancers.