Chapter 17: Regulation of Gene Expression in Prokaryotes

Gene types are distinguished as constitutive (always expressed, like housekeeping genes), inducible (turned on by a substrate, characteristic of catabolic pathways such as lactose utilization), or repressible (turned off by an end product, common in anabolic pathways like tryptophan synthesis). Regulatory strategies fall into two categories: positive control, where an activator protein is needed to initiate gene expression, and negative control, where a repressor protein is needed to shut expression off. These regulator proteins bind to specific sites near promoters, and their activity is mediated by small metabolite effector molecules which cause allosteric transitions that alter the protein’s ability to bind DNA. The operon model, introduced by Jacob and Monod, describes coordinated units of gene expression. The classic lac operon exemplifies a negative inducible system where the repressor protein, encoded by the I gene (a trans-acting, diffusible product), binds to the operator (O 1 ,O 2 ,O 3) in the absence of lactose, blocking transcription. Efficient transcription only occurs when the inducer (allolactose) binds to and inactivates the repressor. Furthermore, the lac operon is subject to catabolite repression, a positive control mechanism mediated by the CAP/cAMP complex which ensures glucose, the preferred energy source, is metabolized first. High glucose levels decrease cAMP, preventing CAP from binding to the promoter and stimulating RNA polymerase. In contrast, the trp operon is a negative repressible system, where tryptophan acts as a co-repressor to activate the repressor, halting transcription initiation. A second critical mechanism regulating the trp operon is attenuation, which causes premature termination of transcription based on the presence of tryptophan; this mechanism relies on the coupling of transcription and translation in prokaryotes, where ribosome movement across a leader peptide region determines the formation of either an anti-termination or a transcription-termination hairpin structure. Finally, posttranscriptional regulation provides fine-tuning through translational control (affecting initiation efficiency) and post-translational control via feedback inhibition, where the end product rapidly inhibits the activity of the first enzyme in a biosynthetic pathway.