Why does a human skin cell differ so dramatically from a liver cell, or a muscle cell, or a neuron? After all, every cell in the body (except gametes) has the same genome -- the same complement of DNA. (We'll ignore somatic mutations for the moment.) So why are these cells' "phenotypes" so different, if their genotype is the same?
The answer, of course, is that in skin cells, some genes are expressed and others aren't. In a liver cell, a different set of genes is expressed. Other genes are expressed (or repressed) only in response to an environmental influence or a signal from another cell. The molecular mechanisms that allow cells to regulate gene expression -- to turning genes on and off -- is the main topic of this chapter.
Before we dig into these molecular mechanisms, though, two important points tie these firmly to the realm of genetics and heritability. First, as we will see, the regulation of a gene is dependent on DNA sequences -- promoters, proximal regulatory elements, distal enhancers, splice sites, etc -- which can themselves be polymorphic. That is, the amount that a gene is expressed is itself a heritable trait, subject to selection just like any other trait.
And secondly, have you ever considered that when a liver cell divides, the two daughter cells look like liver cells -- and not skin cells or neurons? (Similarly, when a skin cell in the same organism divides, its two daugher cells also look like skin cells.) That's because in both cases, the daugher cells are expressing the same set of genes as the parent cell. Patterns of gene expression are heritable. We call the inheritance of these patterns of gene expression epigenetics. We'll examine both genetic and epigenetic control of gene expression as the chapter progresses.
Learning Objectives
If you have mastered the material in this chapter, you should be able to:
Define the following terms used in prokaryotic gene regulation: promoter, transcription factor, inducer, operon, regulon
Describe how transcription factors regulate the transcription of operons
Predict how changes in DNA sequence will affect gene expression
Define the following terms used in eukaryotic gene regulation: chromatin, histone, methylation, alternative splicing, RNA interference (RNAi)
Describe how the following affect gene expression:
Acetylation and deacetylation of chromatin
Methylation of DNA
Alternative splicing
RNAi
Predict how changes in chromatin, DNA methylation, alternative splicing, and RNAi will affect gene expression
The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA.
The DNA of prokaryotes is organized into a circular chromosome supercoiled in the nucleoid region of the cell cytoplasm. Proteins that are needed for a specific function, or that are involved in the same biochemical pathway, are encoded together in blocks called operons. For example, all of the genes needed to use lactose as an energy source are coded next to each other in the lactose (or lac) operon.
Eukaryotic gene expression is more complex than prokaryotic gene expression because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.
Like prokaryotic cells, the transcription of genes in eukaryotes requires the actions of an RNA polymerase to bind to a sequence upstream of a gene to initiate transcription. However, unlike prokaryotic cells, the eukaryotic RNA polymerase requires other proteins, or transcription factors, to facilitate transcription initiation. Transcription factors are proteins that bind to the promoter sequence and other regulatory sequences to control the transcription of the target gene.
RNA is transcribed, but must be processed into a mature form before translation can begin. This processing after an RNA molecule has been transcribed, but before it is translated into a protein, is called post-transcriptional modification. As with the epigenetic and transcriptional stages of processing, this post-transcriptional step can also be regulated to control gene expression in the cell. If the RNA is not processed, shuttled, or translated, then no protein will be synthesized.
After the RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. As previously discussed, the stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.
