"This was our attempt to make sense out of a microarray experiment with hundreds of genes and bring it to an end," says Susan Mango, PhD, associate investigator, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City. That end being the identification of cis-regulatory sites that could dictate some of the tissue cell types within the pharynx of the worm and pulling out a transcription factor that addresses some of the biology, says Mango.

Taking the results of their microarray experiments, which were grouped into clusters of pharyngeal genes based on expression within a common cell type, Mango's team applied an algorithm developed by James Kent, PhD, named Improbizer, to pick out potential cis-regulatory sites.

According to the study, Improbizer searches for motifs in DNA or RNA sequences that occur with unexpected frequency by using a variation of the expectation maximization algorithm. A transcription factor known as DAF-12, bound to one of the five motifs identified that had the most specific and activated expression within the pharyngeal muscles.

"The worm is clearly a good model for understanding questions regarding nutrition, longevity, and fat storage," says Mango. "The DAF-12 protein had been implicated in those processes but the direct targets of DAF-12 were not known." This provides a clue as to how it functions and is in agreement with other data, she says. "It gives us a foot-hold into looking at how worms sense nutritional cues and respond to feeding."

By Elizabeth Tolchin