In contrast, Dr. Amati's group used human cells to identify Myc target genes. The researchers focused on those genes that bind Myc through the consensus "E-box" DNA sequence (CACGTG). Dr. Amati and colleagues used bioinformatics tools to scan the human genome and identify genes containing one or more E-boxes in the proximity of their promoter (the portion of the gene where transcription begins). Of the 1630 gene loci identified, approximately 700 underwent further biochemical characterization to determine which E-box-containing genes bind Myc in vivo. As in flies, the results were surprising.
As Dr. Amati explains, "In addition to identifying 257 genes that are bound by Myc in the human genome, our data also reveals that Myc must bind at least one tenth of all cellular genes or, in other words, several thousand genes. This unexpected degree of complexity is a fundamental feature that is conserved between humans and flies."
Taken together, these two studies provide the most comprehensive enumeration of direct, in vivo Myc targets. The conclusion that Myc binds a large portion of both the fly and human genome dramatically alters previous views of Myc's activity and the complexity of its biological interactions. Rather than consider a limited number of genes to be targets of Myc, it is now apparent that Myc exerts an extremely widespread influence over the vertebrate genome.