Aug. 11, 2006 Research Highlight Biology Medicine / Disease
Getting genomic analysis off to a good start
A massive genomic research effort yields new insights into the structure of mammalian genes
The starting point for every gene’s activity is its promoter, a stretch of DNA where specific proteins can bind to turn a gene on (or keep it turned off). Because of this, techniques for determining the locations of promoters are valuable tools for finding genes in a given region of the genome and for studying conditions under which those genes are active.
One such technique, known as ‘CAGE’, was recently described by Yoshihide Hayashizaki and his colleagues at the RIKEN Genomic Sciences Center in Yokohama. CAGE allows scientists to rapidly collect large numbers of short sequence ‘tags’ that can be used to identify transcription start sites (TSSs), and this data can in turn be used to zero in on promoters.
In new work described in the journal Nature Genetics 1, Hayashizaki’s group has collaborated with an international consortium of researchers, the RIKEN-directed FANTOM-3 project, to apply CAGE to the analysis of the mouse and human genomes, identifying hundreds of thousands of TSSs that could be used to locate likely promoters. According to Hayashizaki, the sheer quantity of data proved surprising. “The number of TSS was definitely much larger than the number of protein-coding genes and the number of reported, known promoters,” he says.
Closer analysis of the data led to the identification of two major promoter classes. For ‘narrow’ promoters, transcription is initiated at very specific genomic sites, and the promoters show strong conservation between mice and humans. For ‘broad’ promoters, however, TSSs are scattered over much larger areas, and the promoters show greater evolutionary change between species. Surprisingly, the ‘narrow’ promoters, which contain specialized protein-binding sequences previously thought to be fundamental features of most mammalian promoters, proved to be much less common than the ‘broad’ promoters that don’t necessarily contain these sequences.
The data from this study has provided a valuable starting point for identifying important structural elements of different promoter types, data that could help scientists predict when individual genes are likely to become active and in which tissues or organs a given gene might be expressed. “This will allow a much more detailed understanding of the expression of genes,” concludes Hayashizaki, “and will open new possibilities to modify their expression for biomedical applications.”
References
- 1. Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J. et al. Genome-wide analysis of mammalian promoter architecture and evolution. Nature Genetics 38, 626–635 (2006). doi: 10.1038/ng1789