Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

400 Chapter 7: Control of Gene Expression
Moreover, the same number can complete the combination for many different
locks. Likewise, the addition of a particular protein can turn on many different
genes.
An example is the rapid control of gene expression by the human glucocorticoid
receptor protein. To bind to its cis-regulatory sequences in the genome, this
transcription regulator must first form a complex with a molecule of a glucocorticoid
steroid hormone, such as cortisol (see Figure 15–64). The body releases this
hormone during times of starvation and intense physical activity, and among its
other activities, it stimulates liver cells to increase the production of glucose from
amino acids and other small molecules. To respond in this way, liver cells increase
the expression of many different genes that code for metabolic enzymes, such as
tyrosine aminotransferase, as we discussed earlier in this chapter (see Figure 7–3).
Although these genes all have different and complex control regions, their maximal
expression depends on the binding of the hormone–glucocorticoid receptor
complex to its cis-regulatory sequence, which is present in the control region of
each gene. When the body has recovered and the hormone is no longer present,
the expression of each of these genes drops to its normal level in the liver. In this
way, a single transcription regulator can rapidly control the expression of many
different genes (Figure 7–38).
The effects of the glucocorticoid receptor are not confined to cells of the liver.
In other cell types, activation of this transcription regulator by hormone also
causes changes in the expression levels of many genes; the genes affected, however,
are usually different from those affected in liver cells. As we have seen, each
cell type has an individualized set of transcription regulators, and because of
combinatorial control, these critically influence the action of the glucocorticoid
receptor. Because the receptor is able to assemble with many different sets of celltype-specific
transcription regulators, switching it on with hormone produces a
different spectrum of effects in each cell type.
Differentiated Cells Maintain Their Identity
Once a cell has become differentiated into a particular cell type, it will generally
remain differentiated, and all its progeny cells will remain that same cell type.
Some highly specialized cells, including skeletal muscle cells and neurons, never
divide again once they have differentiated—that is, they are terminally differentiated
(as discussed in Chapter 17). But many other differentiated cells—such as
glucocorticoid
receptor in
absence of
glucocorticoid
hormone
GENES EXPRESSED AT LOW LEVEL
gene 1
gene 2
gene 3
glucocorticoid
hormone
gene 1
gene 2
gene 3
GENES EXPRESSED AT HIGH LEVEL
Figure 7–38 A single transcription
regulator can coordinate the expression
of many different genes. The action of
the glucocorticoid receptor is illustrated
schematically. On the left is a series
of genes, each of which has various
transcription regulators bound to its
regulatory region. However, these bound
proteins are not sufficient on their own
to fully activate transcription. On the
right is shown the effect of adding an
additional transcription regulator—the
glucocorticoid receptor in a complex with
glucocorticoid hormone—that has a cisregulatory
sequence in the control region
of each gene. The glucocorticoid receptor
completes the combination of transcription
regulators required for maximal initiation
of transcription, and the genes are now
switched on as a set. When the hormone
is no longer present, the glucocorticoid
receptor dissociates from DNA and the
genes return to their pre-stimulated levels.