Regulation of gene expression

Every cell in your body has the same genes, yet a skin cell and a nerve cell are very different, because each switches on only the genes it needs. Turning genes on and off is gene regulation. It can happen at many stages (chromatin, transcription, RNA processing, transport, translation), but the most important control point is the start of transcription.

Some genes are always on, because the cell always needs them: housekeeping (constitutive) genes, such as those for the citric acid cycle. Most other genes are regulated, switched on only when needed.

In bacteria, genes for related jobs are grouped in an operon, with one promoter and an operator (a switch). A separate regulator gene, outside the operon, makes a repressor protein. There are two kinds of operon:

• Inducible: normally off, switched on by a substrate (the inducer).
• Repressible: normally on, switched off by an end product (the co-repressor). For example, the enzymes for making histidine are switched off when histidine is supplied.

Jacob and Monod (1961) described the lac operon, for using the sugar lactose. It has three structural genes: lacZ (β-galactosidase, which splits lactose), lacY (permease, which lets lactose into the cell) and lacA (transacetylase), controlled by the repressor made by lacI.

• No lactose: the repressor sits on the operator and blocks the road, so RNA polymerase cannot transcribe the genes (negative control).
• Lactose present: a form of it, allolactose, binds the repressor, which lets go. The three genes are transcribed together into one polycistronic mRNA.
• When the lactose is used up, the repressor binds again and the operon switches off.