14.8 Gene Expression

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14.8.3

Prokaryotic Transcriptional Regulation

The main problem to be solved in prokaryotes is that different genes need to be active

under different external conditions and during successive processes in the cell cycle.

The primary control mechanism is via promoter sites situated upstream of that part of

the DNA that will ultimately be translated into protein (cf. Fig. 14.3). For genes that

need to be essentially constantly transcribed (the so-called housekeeping genes; i.e.,

those coding for proteins that are constantly required, such as those assembling the

RNAp complex), there is no hindrance to RNAp binding to the initiation zone and

beginning its work; only in exceptional circumstances might it be necessary to arrest

production, whereupon a protein (called a repressor) will bind to a sequence within

the initiation zone (often immediately preceding the protein coding sequence) called

the promoter, preventing the RNAp from binding to the DNA (Sauvageot’s princi-

ple). Sometimes, the transcription factor is simply the gene product. Conversely, for

proteins seldom required, such as an enzyme for detoxifying a rarely encountered

environmental hazard, the appropriate RNAp will normally have no affinity for the

initiation zone, but should the toxin penetrate the cell, it will trigger the binding of

a promoting (rather than inhibiting) transcriptional factor (called an activator) to the

promoter site, whereupon the RNAp can bind and start its work.

Sometimes, the translation of several (functionally related) genes is controlled by

a single promoter. These structures of genes and promoter are called operons.

14.8.4

Eukaryotic Transcriptional Regulation

The requirements for gene regulation in eukaryotes are more complex, not least

because, in a multicellular organism, as it differentiates many genes need to be

permanently inactivated. Eukaryotes therefore have much richer possibilities for

regulating transcription than prokaryotes. The mechanisms fall into five categories:

1. DNA methylation;

2. Chromatin conformation;

3. Binding of complementary (“antisense”) RNA to key sites on the DNA;

4. Promoter sites and transcription factors (activators and repressors) as in prokary-

otes ⁵²;

5. Competition for transcription factors by promoter sites on pseudogenes.

52 While a single RNAp operates in prokaryotes, there are at least three distinct ones in eukaryotes,

accompanied by a host of “general transcription factors”, all of which considerably increases the

possible combinations of regulatory agents.