Have a heart: Turn on just a single gene

There’s no single gene for being kind, but there seems to be one for being heartless.

A lone gene appears to act as the master switch in embryonic heart formation, researchers report in the June 29 Cell. When mutated, the gene makes an impaired version of its protein, which fails to turn on other heart genes, so no heart forms.

“There has been intense interest in identifying genes responsible for heart formation,” says Eric N. Olson of the University of Texas Southwestern Medical Center in Dallas. The attention stems from the frequency of birth defects involving the heart and the poor ability of the adult heart to regenerate after damage (see article “Telltale Heart” in this issue).

Olson and his team set out to find a gene that kicks the heart-generation process into motion. “Specifically, our greatest hope was that we would find a master gene,” says Olson.

Instead of looking for the gene in the lab, Olson went to the library–the gene library, that is. He and his colleagues at UT Southwestern and the University of Arizona College of Medicine in Tucson hunted through mouse- and human-genome databases in search of DNA sequences resembling genes already known to function in the heart.

They found about 20 novel sequences that fit their criterion. Then, they experimented with mice to find out whether any of the sequences encoded proteins active in the heart. The most promising one encoded a previously unknown protein that homed in on a gene region already known to be packed with heart-muscle and skeletal-muscle genes and guided the cell’s protein-production machinery to that site.

The team named the newly identified protein myocardin, after the word for heart muscle. To test its importance, Olson and his team injected an impaired version of the gene into frog embryos before the first heart cells had formed. In most cases, other genes encoding heart proteins never turned on. The researchers believe that the gene produced large numbers of bad copies of myocardin, drowning out the frog’s normal signal for heart formation.

Robert J. Schwartz of Baylor College of Medicine in Houston calls this work “incredibly exciting and important.” Schwartz works with other genes involved in heart formation, but he says that Olson’s team has discovered what appears to be the trigger for the other heart genes.

This gene may, however, work in synergy with several other important genes, Schwartz speculates. He notes, “Just as there are multiple ways to skin a cat, there are multiple ways to regulate genes.”

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