AN OVERVIEW OF GENE EXPRESSION HOW TRANSCRIPTIONAL SWITCHES WORK THE MOLECULAR MECHANISMS THAT CREATE SPECIALIZED CELL TYPES POST-TRANSCRIPTIONAL CONTROLS
Control of Gene Expression
An organism’s DNA encodes all of the RNA and protein molecules that are needed to make its cells. Yet a complete description of the DNA sequence of an organism—be it the few million nucleotides of a bacterium or the few billion nucleotides in each human cell—does not enable us to reconstruct the organism any more than a list of all the English words in a dictionary enables us to reconstruct a play by Shakespeare. We need to know how the elements in the DNA sequence or the words on a list work together to make the masterpiece. In cell biology, the question comes down to gene expression. Even the simplest single-celled bacterium can use its genes selectively—for example, switching genes on and off to make the enzymes needed to digest whatever food sources are available. And, in multicellular plants and animals, gene expression is under even more elaborate control. Over the course of embryonic development, a fertilized egg cell gives rise to many cell types that differ dramatically in both structure and function. The differences between a mammalian neuron and a lymphocyte, for example, are so extreme that it is difﬁcult to imagine that the two cells contain the same DNA (Figure 8–1). For this reason, and because cells in an adult organism rarely lose their distinctive characteristics, biologists originally suspected that genes might be selectively lost when a cell becomes specialized. We now know, however, that nearly all the cells of a multicellular organism contain the same genome. Cell differentiation is instead achieved by changes in gene expression. Hundreds of different cell types carry out a range of specialized functions that depend upon genes that are only switched on in that cell type: for
Control of Gene Expression example, the cells of the pancreas make the protein hormone insulin, while the cells of the pancreas make the hormone glucagon; the lymphocytes of the immune system are the only cells in the body to make antibodies, while developing red blood cells are the only cells that make the oxygen-transport protein hemoglobin. The differences between a neuron, a lymphocyte, a liver cell, and a red blood cell depend upon the precise control of gene expression. In each case the cell is using only some of the genes in its total repertoire. In this chapter, we shall discuss the main ways in which gene expression is controlled in bacterial and eucaryotic cells. Although some mechanisms of control apply to both sorts of cells, eucaryotic cells, through their more complex chromosomal structure, have ways of controlling gene expression that are not available to bacteria.
AN OVERVIEW OF GENE EXPRESSION
How does an individual cell specify which of its many thousands of genes to express? This decision is an especially important problem for multicellular organisms because, as the animal develops, cell types such as muscle, nerve, and blood cells become different from one another, eventually leading to the wide variety of cell types seen in the adult. Such differentiation arises because cells make and accumulate different sets of RNA and protein molecules: that is, they express different genes.
The Different Cell Types of a Multicellular Organism Contain the Same DNA As discussed above, cells have the ability to change which genes they express without altering the nucleotide sequence of their DNA. But how do we know this? If DNA were altered irreversibly during development, the chromosomes of a differentiated cell would be incapable of guiding the development of the whole organism. To test this idea, a nucleus from a skin cell of an adult frog was injected into a frog egg whose own nucleus had been removed. In at least some cases the egg developed normally into a tadpole, indicating...