THE LIVING WORLD
Unit Three. The Continuity of Life
12.7. Controlling Transcription from a Distance
In eukaryotes, transcription is considerably more complex, and the amount of DNA involved in regulating eukaryotic genes is much greater.
Eukaryotic Transcription Factors
Eukaryotic transcription requires not only the RNA polymerase molecule, but also a variety of other proteins, called transcription factors, that interact with the polymerase.
Basal transcription factors are necessary for the assembly of a transcription apparatus and recruitment of RNA polymerase to a promoter. While these factors are required for transcription to occur, they do not increase the rate of transcription above a low rate, the so-called basal rate. These factors, colored green in figure 12.16, all come together to form the initiation complex. This is clearly much more complex than a bacterial RNA polymerase, which is a single enzyme protein.
The initiation complex, once assembled, will not achieve transcription at a high level without the participation of other gene-specific factors. The number and diversity of these specific transcription factors, colored tan in figure 12.16, is overwhelming. Multicellular organisms control which genes are expressed by regulating which specific transcription factors are available at a particular time and place.
Figure 12.16 Formation of a eukaryotic initiation complex.
The basal transcription factors (green) bind to the promoter region of the DNA and form an initiation complex. A number of specific transcription factors (tan) bind to the basal transcription factor complex (the initiation complex) and together recruit the RNA polymerase molecule to the promoter.
While prokaryotic gene control regions, such as the operator, are positioned immediately upstream of the coding region, this is not true in eukaryotes. It turns out that far away sites called enhancers can have a major impact on the rate of transcription. Enhancers are nucleotide sequences where specific transcription factors, acting as activators, bind the DNA. The ability of enhancers to act over large distances is accomplished by DNA bending to form a loop. In figure 12.17, an activator binds to the yellow-colored enhancer far from the promoter. The DNA loops, bringing the activator in contact with the RNA polymerase/initiation complex so that transcription can begin.
Figure 12.17. How enhancers work.
The activator binding site, or enhancer, is often located far from the gene. The binding of an activator protein brings the enhancer in contact with the gene.
Complicating the process even more, several different additional transcription factors may modulate the action of a particular specific transcription factor. These coactivators and mediators act by first binding the transcription factor, and then binding to the transcription apparatus.
Tying It All Together
How can we make sense of this extremely complicated situation? Virtually all genes that are transcribed by RNA polymerase in eukaryotes need the same group of basal factors to assemble an initiation complex, but its ultimate level of transcription depends in each instance on the other specific factors involved that make up a transcription complex. This kind of combined gene regulation leads to great flexibility in the control of gene expression. It provides the cell the ability to produce finely graded responses to the many environmental and developmental signals that it may receive. The eukaryotic cell achieves a higher level of control because of the interaction of a large number of protein regulatory elements (figure 12.18). This control is more sophisticated but not fundamentally different from the integration achieved by the prokaryotic lac operon using two regulatory proteins.
Figure 12.18. Interactions of various factors within the transcription complex.
All specific transcription factors bind to enhancer sequences that may be distant from the promoter. These proteins can then interact with the initiation complex by DNA looping to bring the factors into proximity with the initiation complex. As detailed in the text, some transcription factors, activators, can directly interact with the RNA polymerase II or the initiation complex while others require additional coactivators. The electron micrographs are of the bacterial activator NtrC. When it binds to an enhancer, you can see how this causes the DNA to loop over to a distant site where RNA polymerase is bound, activating transcription. While such enhancers are rare in prokaryotes, they are common in eukaryotes.
Key Learning Outcome 12.7. Transcription factors and enhancers give eukaryotic cells great flexibility in controlling gene expression.