Regulation of gene expression: the lac operon

In eukaryotes gene expression can be regulated at transcription, at processing (splicing), at transport of mRNA from nucleus to cytoplasm, and at translation.

Genes are switched on and off as the cell's needs change. For example, E. coli makes beta-galactosidase, which breaks lactose into galactose and glucose, only when lactose must be used; without lactose it does not need the enzyme.

In prokaryotes the main control point is the rate of transcription initiation. The promoter's accessibility to RNA polymerase depends on proteins binding operator sequences; these regulatory proteins can be activators or repressors.

An operon is a set of genes transcribed together as a polycistronic unit under a common promoter and regulatory genes. Examples include the lac, trp, ara, his and val operons. François Jacob and Jacques Monod first described a transcriptionally regulated system, the lac operon.

The lac operon has a regulatory i gene (the i comes from inhibitor, not inducer) and three structural genes: z codes beta-galactosidase, y codes permease, which increases the cell's permeability to β-galactosides, and a codes transacetylase.

The repressor is made by the i gene all the time (constitutively). If no inducer is present, the repressor binds the operator, which stops RNA polymerase from transcribing the operon.

Lactose (or allolactose) is the inducer. It binds to and inactivates the repressor, so the repressor cannot bind the operator, RNA polymerase reaches the promoter and the structural genes are transcribed.

A very low basal level of lac operon expression is always present in the cell; without some permease, lactose could not enter the cell to induce the operon.

Because a repressor switches the operon off, this control is called negative regulation.