Prokaryotic cells often regulate gene expression by controlling whether RNA polymerase initiates transcription. Genes whose products participate in the same cellular task can be grouped into an operon and transcribed together from one promoter into a single RNA containing several protein-coding regions.

Regulatory DNA sequences and DNA-binding proteins control access to transcription.

• A repressor lowers transcription when bound to its regulatory site.
• An activator increases transcription by helping RNA polymerase initiate.
• A small molecule can alter a regulator's activity by binding to it.

Negative and positive control

In negative regulation, a repressor prevents or reduces transcription. Removing or inactivating the repressor increases expression.

In positive regulation, an activator promotes transcription. Losing activator function decreases expression.

A gene can be subject to both forms of control at once.

Example: logic of the lac operon

The bacterial lac operon contains genes whose products help cells use lactose. Its regulation responds to both lactose availability and the availability of a preferred carbon source such as glucose.

A simplified logic is:

• when lactose is absent, a repressor strongly suppresses transcription;
• when lactose is available, a lactose-derived signal reduces repression;
• when glucose is scarce, an activator can further increase transcription.

Thus the strongest expression occurs when lactose is available to use and glucose is scarce.

The important lesson is not the names of the lac components but the logic: regulatory proteins convert environmental information into changes in transcription initiation.

Operons coordinate several genes

Because multiple coding regions can share one promoter, changing transcription of an operon can coordinately change production of several proteins. This differs from the common eukaryotic arrangement in which protein-coding genes are usually transcribed as separate mRNAs.

Prokaryotic transcriptional regulation therefore provides a compact example of gene control by cis-regulatory DNA sequences—sequences acting on the DNA molecule on which they reside—and diffusible regulatory proteins that recognize those sequences.