Gene Regulation

Here's a question that every high-school biology student ought to ask: "if every cell in our body has the same DNA [which is almost true], why are they so different?" Understanding how different cells employ different parts of the common genome, turning some genes "on" and others "off," for example, is a long-standing problem in biology. As is typical for biology, there are many correct answers, some only now being elucidated.

Different cells have characteristic "signatures" of genetic activity. A neuron is a neuron because certain sets of genes, like those that specify proteins used in synapses, are active, while genes involved in synthesizing bile, for example, are not. The pattern also changes though the various stages of the cell cycle that lead to cell division. But such differences are only the tip of the gene-regulation iceberg.

A single-cell zygote develops into a complex multi-cellular organism like you or me through an intricate choreography that activates and represses genes in the appropriate cells at the appropriate times. This gene regulation is coordinated in time, as the activity of one gene triggers event that turn another on or off. It is also coordinated in space, as gene activity in one cell or region creates chemical signals that affect nearby cells. Perhaps it's not too surprising that the complex "network" of genes turning each other on and off can give rise to complicated patterns and time and space. But it is still close to miraculous that this complex process produces such complex creatures--with fingernails, bile ducts, and neural circuits that specialize in speech perception--with such astonishing robustness. (It fails frequently, but it's amazing that it works at all.)

Normally developing body cells change their patterns of expression irreversibly: once they have differentiated from a more general-purpose cell to a specialized cell, they don't go back again. This irreversibility is a somewhat surprising property of the interaction network, and presumably helps to assure proper development. Until recently, therefore, researchers looking to generate new cells for either research or therapeutic purposes had to isolate "stem cells" that had not yet gone through this irreversible differentiation. The most versatile such cells come from embryonic tissue only a few days after fertilization. These embryonic stem cells are still very important, but in the past few years researchers have successfully turned back the clock on fully differentiated skin cells, for example, apparently giving them all the versatility of embryonic stem cells.

Cancer cells also turn back the clock, activating genes that normally function only in early development. Some cancers, for example, turn on genes that induce nearby tissue to build blood vessels to supply the growing cancer. In ordinary cells, the genetic networks that enable this activity are present but inactive after they do their work in the growing embryo. The ability of cancer cells to re-activate these dormant cellular programs is a key to their success, but also gives researchers critical insight into the ways genes are regulated.

In future posts I will discuss various molecular mechanisms of gene regulation.