How gene expression is regulated? - Module 4 Reading / Watching

Francois Jacob & Jacques Monod. studied the mechanisms of transcriptional regulation in E. coli.   

The lac operon consists of  two main components  namely  the regulatory genes and  structural genes .

The structural genes

The structural genes are lax Z, lac Y and lac A. These encode the three enzymes involved in lactose metabolism ; These are  lac Z encodes an enzyme calledβ-galactosidase, which digests lactose into its two constituent sugars namely  glucose and galactose.  lac Y encodes the enzyme called  permease that helps to transfer lactose into the cell and lac A  encodes  trans-acetylase; the relevance of which in lactose metabolism is not clearly understood.

The regulatory genes 

In addition to the three protein-coding genes, the lac operon contains short DNA sequences that do not encode proteins,  These sequences are called P (promoter), O (operator), and CBS (CAP-binding site) . These are  binding sites for proteins involved in transcriptional regulation of the operon.

 These sequences are called cis-elements as they are located on the DNA of  the genes they regulate. On the other hand, the proteins that bind to these cis-elements are called trans-regulators . These are diffusible molecules and are not necessarily need to be encoded on the same piece of DNA as the genes they regulate.

One of the major trans-regulators of the lac operon is encoded by lacI. which codes for the lac I protein. Four identical molecules of lacI proteins assemble together to form a homotetramer called a repressor.

Negative regulation of the Lac Operon 

In the absence of Lactose and when glucose is available in the medium , the repressor binds to two operator sequences adjacent to the promoter of the lac operon. Binding of the repressor prevents RNA polymerase from binding to the promoter . Therefore, the operon will not be transcribed when the operator is occupied by a repressor. This is called negative regulation.

Positive Regulation 

When  the level of glucose in the medium is   very low or non-existent and when lactose is available in the medium, the lac operon is induced to express the genes i.e., Only when glucose is absent and lactose is present will the lac operon be transcribed .When lactose is present, its metabolite, allolactose, binds to the lac repressor and changes its shape so that it cannot bind to the lac operator to prevent transcription.  This is referred to as positive regulation

 It should be mentioned that the lac operon is transcribed at a very low rate even when glucose is present and lactose absent.