Females' potentially toxic double dose of the X chromosome appears to be offset by a molecular "dimmer switch."

DCC recruiting fragments (green, arrows) with multiple A motifs recruit the DCC (red) so strongly in hermaphrodite nuclei (blue), they pull complexes away from X chromosomes. Reducing A motif number by mutation decreases recruitment strength, and DCC binding returns to X.).

Sugar and spice and X chromosome twice—that's what girls are made of, despite the fact that this double dollop of X chromosomes can be deadly for females of any species. HHMI investigator Barbara J. Meyer and her colleagues at the University of California, Berkeley, study how the roundworm, Caenorhabditis elegans, compensates for that second dose.

It turns out that in a C. elegans hermaphrodite (a female that makes sperm as well as eggs), gene expression from each X chromosome gets turned down by half—a feat accomplished with a sort of molecular "dimmer switch," Meyer's group has shown. Dubbed the dosage compensation complex (DCC), it covers the length of both X chromosomes but no other chromosomes.

To understand just how the DCC represses genes, Meyer's group tackled a more fundamental question: How does the DCC distinguish an X chromosome from other chromosomes in the first place? As they reported in the November 30, 2006, issue of Nature, the researchers have made an important discovery that reveals much of the answer. After chopping an X chromosome into small pieces and introducing them into C. elegans hermaphrodites one at a time, they identified numerous fragments that could recruit the DCC proteins.

"When we dissected the recruiting fragments further, we narrowed them down to really tiny pieces—only 33 nucleotides in one case," Meyer says. Each site contains patterns of two different nucleotide stretches, termed A and B motifs. Surprisingly, both motifs also occur on the other chromosomes. "But we noticed that each recruitment site contained multiple copies of these motifs. And it's the clustering of these motifs on the X chromosomes that seems to matter," Meyer says.

Meyer speculates that cells may use similar principles to accomplish other chromosome-wide tasks such as DNA replication, chromosome segregation, and other forms of coordinated gene regulation.

Image courtesy of Patrick McDonald, Jessica Gunther, Judith Jans / Meyer lab