Gene Regulation

The genome is the sum total of all the genes present in an organism. For the organism to function properly, not all genes in the genome can be active at all times. Similarly, not all cells of a multicellular organism express all the genes present in its genome. For example, human pancreatic cells do not make hemoglobin, but they do produce insulin. On the other hand, progenitors of red blood cells synthesize hemoglobin but do not make insulin. Also, human embryos produce a special hemoglobin that is not found in the adult. How is this possible, knowing that all cells in the human body contain the same DNA? The answer is that cells can turn genes on and off to regulate which genes are expressed in what cells and when. We say that the insulin gene is turned off in all cells except specialized pancreatic cells, whereas the gene coding for embryonic hemoglobin is turned on during fetal life but is turned off later on.

Gene regulation is very complicated and only partially understood. It takes place in all living organisms, from bacteria to humans. Often, whether a gene is active (transcribed) or inactive (not

Figure 4.9 Regulation of Transcription. A. Definitions of symbols used in this figure. B. A portion of DNA diagrammed to show that when RNA polymerase binds the promoter region, transcription can proceed. C. If a protein factor binds to the promoter region of the DNA, RNA polymerase cannot bind and thus the protein factor prevents transcription of the gene.

Figure 4.9 Regulation of Transcription. A. Definitions of symbols used in this figure. B. A portion of DNA diagrammed to show that when RNA polymerase binds the promoter region, transcription can proceed. C. If a protein factor binds to the promoter region of the DNA, RNA polymerase cannot bind and thus the protein factor prevents transcription of the gene.

transcribed) depends on interactions between the gene's promoter and protein factors present in a given type of cells. Basically, when these protein factors are present, they bind to the promoter region and physically block it (figure 4.9). Under these circumstances, RNA polymerase has no access to the promoter and hence cannot transcribe the gene. Without mRNA production, the gene cannot pro-

duce its protein, and thus the gene is turned off. Conversely, other factors can bind to this blocking protein factor and prevent it from blocking the promoter. In this case, RNA polymerase has access to the promoter. The gene is then transcribed, its mRNA subsequently translated, and the gene is turned on. Cells contain thousands of such factors that act in concert to fine-tune gene activity.

Embryonic Stem Cells Exhibit a Special Type of Gene Regulation Embryonic stem cells provide an interesting example of gene regulation. Embryos contain stem cells, cells that can be coaxed into producing any and all types of human tissue. By definition, a young embryo contains cells that will eventually produce all the organs found in a complete human being. In other words, the cells of a young embryo are pluripotent, and can differentiate into any cell type, such as brain, heart, or muscle cells, and so forth. Researchers are keen on understanding what triggers embryonic stem cells to differentiate into specialized tissues. Once these mechanisms are understood, it will be possible to regenerate organs that are faltering due to accident or illness. The idea of repairing the spinal cord of paraplegic and quadriplegic individuals comes to mind. For now, suffice it to say that not much is known about the signals that allow embryonic stem cells to differentiate into various organs. One thing is clear, however. Before differentiation, embryonic stem cells express a large collection of genes; many of their genes are "on." As the cells differentiate, many genes are progressively turned "off," and specialized genes, which are only expressed in differentiated organs, are turned "on."

Box 4.1 Why People Are Saving Their Babies' Cord Blood

Because stem cells are capable of turning into a variety of different specialized cells, such as brain cells or blood cells, they hold great promise for the treatment of diseases such as Alzheimer's, heart disease, and a variety of cancers. Cells in an early embryo, just by their very nature, can give rise to all the cells in the body. However, embryonic stem cells are controversial because their use necessitates killing the embryo.

Another source of stem cells is the umbilical cord blood. These stems cells can give rise to cells in the blood including red blood continued on next page

Box 4.1 continued cells, which carry oxygen, white blood cells, which are cells of the immune system, and platelets, which are involved in blood clotting. Similar stem cells are found in adult bone marrow. But the stem cells in the cord blood are younger and thus have a higher chance of providing a good match. Cord blood also has a higher number of stem cells. Until recently, the blood in the umbilical cord was routinely discarded with the placenta. We now can collect and store the stem cells from cord blood. The procedure requires that cord blood be collected soon after the umbilical cord is clamped off. Special processing and freezer storage makes the stem cells available years later to the individual from which the cord blood was collected. Although not all diseases treatable by stem cells can be treated with cord-blood stem cells, a large number of diseases associated with blood, immune systems, and other metabolic diseases can be treated with cord-blood stem cells.

In the United States, cord blood may be donated to many public blood banks, including the American Red Cross, for use by any one. The National Institutes of Health also maintain a cord-blood bank. Donating your baby's blood to these two cord-blood banks does not cost the donor. Alternatively one can pay approximately $2,000 to store the baby's cord blood in a private cord bank, Cord Blood Registry (, and have it available for the donor's use.

One report of how cord blood can save a life was reported on CBS's 60 Minutes II. This is the story of Keone Penn, a teenager with sickle-cell anemia. This is a disease of hemoglobin in the red blood cells. In the past, the only possibility for a cure was a bone marrow transplant. However, for Keone, there was not a good donor match. But doctors thought that cord blood might help to cure Keone of his sickle-cell disease. It would be easier to find a good match of cord blood, and cord blood has higher numbers of stem cells than even bone marrow. Fortunately for Keone, a good match was found in the New York Public Blood Bank. His own bone marrow stem cells with the sickle-cell gene were killed with chemotherapy, then he received the matching cord blood, which

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