The Regulation of the lac Operon

Gene expression of lactose-digesting genes is controlled by the lac operon that accounts for varying amounts of lactose or glucose in the cell.

Shelby Bradford, PhD
| 4 min read

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Top: A strand of DNA with the following segments from the lac operon highlighted: lacI (red), Operator 3 (blue), CRP binding site (C, yellow), Promoter 1 (green), Promoter 2 (green), Operator 1 (blue), lacZ (orange), Operator 2 (blue), lacY (pink), lacA (purple). Bottom: Proteins of the lac operon: beta-galactosidase (orange), lactose permease (pink), galactoside acetyltransferase (green), Lac repressor (red), RNA polymerase (blue), cAMP receptor protein, CRP (yellow).
modified from © istock.com, VanReeel, selvanegra, vdvornyk; stock.adobe.com, molekuul.be; designed by erin lemieux

The genes and important sequences for the regulation of the lac operon are organized such that several mediators can fine tune expression of the three genes in the operon itself—lacZ, lacY, and lacA. The gene lacI, which encodes the lac repressor, LacI, sits outside the operon and is constitutively expressed. A cyclic adenosine monophosphate (cAMP) receptor protein (CRP) binding site (C) sits in front of the promoter region where there are two potential RNA polymerase binding sites (P1 and P2). CRP controls the binding of RNA polymerase between P1 and P2 by binding C. Finally, three operator regions, O1, O2, and O3, are spaced through the DNA region to modulate LacI binding and overall operon repression.

Leaky Repression

Glucose available, lactose unavailable. A segment of DNA showing Lac repressor bound to the blue operator region. RNA polymerase is inhibited from regular binding. Only a single beta-galactosidase, galactoside acetyltransferase, and lactose permease is shown.
modified from © istock.com, VanReeel, selvanegra, vdvornyk; stock.adobe.com, molekuul.be; designed by erin lemieux

When glucose, but not lactose, is available in the cell, the LacI binds to the O1 sequence, preventing RNA polymerase from binding to the promoter region. However, due to protein kinetics, a small amount of the lac operon genes can be expressed if the polymerase binds when one repressor releases the DNA before another binds.

Strong Activation

Glucose unavailable, lactose available. A strand of DNA with CRP bound on C and RNA polymerase bound to Promoter 1. Allolactose (grey sphere) is attached to Lac repressor. Three of each of the lac operon gene proteins are shown.
modified from © istock.com, VanReeel, selvanegra, vdvornyk; stock.adobe.com, molekuul.be; designed by erin lemieux

If glucose becomes unavailable but lactose is present, then allolactose (grey sphere) binds LacI, releasing it from the operator. cAMP, produced in the absence of glucose, attaches to CRP, prompting its binding to the C site. This directs the RNA polymerase to sit on the P1 site, which promotes robust expression of the lac operon to facilitate lactose digestion.

Tight Repression

Glucose Available, lactose unavailable. A segment of DNA with the DNA looped. Lac repressor is attached to two operator sites, preventing any RNA polymerase binding or lac operon gene expression.
modified from © istock.com, VanReeel; stock.adobe.com, molekuul.be; designed by erin lemieux

The repression of the lac operon in the absence of lactose can be improved through DNA looping, in which LacI binds to O1 and a second operator sequence, either O2 or O3. This increases the local concentration of LacI, reducing transient expression that occurs when only free-binding lac repressor is available.1

Weak Activation

Glucose available, lactose available. A segment of DNA with RNA polymerase bound to Promoter 2. Allolactose binds Lac repressor. Two of each of the lac operon gene proteins are shown.
modified from © istock.com, VanReeel, selvanegra, vdvornyk; stock.adobe.com, molekuul.be; designed by erin lemieux

When glucose and lactose are both available, allolactose releases LacI from the operator, allowing binding of the RNA polymerase. However, in the absence of cAMP to permit CRP binding, the polymerase binds either P1 or P2 and does not remain on the DNA as effectively, leading to low expression of the lac operon genes.

Read the full story.

  1. Vilar JMG, Leibler S. DNA looping and physical constraints on transcription regulation. J Mol Biol. 2003;331(5):981-989.

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Meet the Author

  • Shelby Bradford, PhD

    Shelby Bradford, PhD

    Shelby is an assistant editor for The Scientist. She earned her PhD from West Virginia University in immunology and microbiology and completed an AAAS Mass Media fellowship.

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