Fingering the right genes in development.

Proteins called transcription factors serve as the sergeants of the genetic army. They tell genes when to turn on, when to turn off, and when to stand silently at attention.

Since the early days of molecular genetics, researchers have predicted that each transcription factor controls a separate platoon of related genes. If not, the scientists reasoned, the resulting army would have as many sergeants as soldiers - making for a very unwiedly state of affairs. However, no one could explain how transcription factors - which must match up to chemical similarities in their subordinate genes in order to function - could recognize and direct the activities of more than one gene.

Several recent studies now suggest that at least some types of transcription factors come in a variety of slightly different forms, with affinities for different genes. The newest report, in the Sept. 25 SCIENCE, indicates that a given type of transcription factor can vary during the development of an organism, turning some genes on and others off in successive stages of the organism's life.

A group of researchers led by Fotis C. Kafatos of Harvard University studied the gene that carries the blueprint for making the outermost layer, or shell, of a fruit fly egg. Kafatos - who also holds a position at the University of Crete in Greece - and his colleagues found that female embryos, pupae, and adult flies each possess a different form of the transcription factor that regulates this gene. Males have yet another form of the same transcription factor, they discovered.

Kafatos' group had previously found that the transcription factor belongs to a class of proteins known as zinc fingers. These proteins, first discovered in 1985, consist of finger-like loops held together by zinc atoms. Each finger in these transcription factors recognizes and binds to a specific region of a gene's DNA.

Kafatos and his colleagues found that the eggshell transcription factor made by fruit fly pupae has one more zinc finger than do forms of the protein made during other stages of the fruit fly life cycle. Moreover, this pupal transcription factor does not bind to the same DNA sequences as the transcription factor produced by embryos or adults, the researchers found.

"The [eggshell transcription factor] protein has a different combination of zinc fingers at different developmental stages," concludes Tien Hsu, a member of the Kafatos group. He suggests that this finger-swapping ability allows such transcription factors to control more than one gene.

Nick Hastie of the Medical Research Council Human Genetics Unit at the Western General Hospital in Edinburgh, Scotland, suggests that alterations in zinc-finger transcription factors may also underlie several cancers and developmental disorders. Earlier this year, he and colleagues described studies of the gene responsible for Wilms' tumor, an inherited kidney cancer in children.

In the July 10 SCIENCE, Hastie's team reported that the gene directs the production of two slightly different forms of a zinc-finger transcription factor. An earlier paper in the May NATURE GENETICS reported that different forms of this transcription factor can also cause birth defects of the kidneys and gonads.