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.
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 receptor in absence of glucocorticoid hormone
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.
fibroblasts, smooth muscle cells, and liver cells—will divide many times in the life of an individual. When they do, these specialized cell types give rise only to cells like themselves: smooth muscle cells do not give rise to liver cells, nor liver cells to fibroblasts.
For a proliferating cell to maintain its identity—a property called cell memory—the patterns of gene expression responsible for that identity must be remembered and passed on to its daughter cells through subsequent cell divisions. Thus, in the model we discussed in Figure 7–33, the production of each transcription regulator, once begun, has to be continued in the daughter cells of each cell division. How is such perpetuation accomplished?