Regulation of Gene Expression — The Lac Operon

A cell contains many more genes than it needs to have switched on at any given moment, and expressing every gene constantly, regardless of whether its product is actually needed, would be a wasteful use of a cell's limited energy and resources. Gene expression is therefore regulated — turned on or off, or turned up or down — at various points, of which the most fundamental and best-studied point of control is transcriptional regulation, i.e., regulating whether or not a particular gene is even transcribed into RNA in the first place. The classic, foundational model system for understanding this kind of regulation is the lac operon of the bacterium Escherichia coli, first described by François Jacob and Jacques Monod, whose "operon model" earned them a share of the 1965 Nobel Prize.

An operon is a cluster of structural genes that are transcribed together, as a single continuous mRNA molecule, under the shared control of one common promoter and one common regulatory (operator) sequence. The lac operon of E. coli regulates the metabolism of the sugar lactose and consists of three structural genes, transcribed together as a single mRNA: lacZ, which codes for the enzyme beta-galactosidase, responsible for hydrolysing the disaccharide lactose into its two constituent monosaccharides, glucose and galactose; lacY, which codes for permease, a membrane transport protein that increases the permeability of the bacterial cell membrane to lactose, allowing lactose to be actively taken up into the cell; and lacA, which codes for transacetylase, an enzyme whose precise metabolic role in lactose utilisation is comparatively less well understood.

Regulation of the lac operon depends on a separate regulatory gene, called the lac i gene (the "i" stands for "inhibitor"), located just upstream of the operon's own promoter; the lac i gene is constitutively (continuously) transcribed and translated, independently of the operon's own on/off state, to produce a protein called the lac repressor. In the ABSENCE of lactose in the bacterium's growth medium, the lac repressor protein binds tightly to a specific DNA sequence, the operator, which lies between the operon's promoter and its structural genes; a repressor bound at the operator physically obstructs RNA polymerase from moving forward past the operator to transcribe the structural genes, so the operon remains switched OFF (the structural genes are not transcribed, and the corresponding lactose-metabolising enzymes are not made) — an economical arrangement, since making enzymes to metabolise a sugar the cell has no access to would simply waste resources. …