Wednesday, December 06, 2006

Image Enhancers!

That must have been the command that went out at the Joint Genome Institute, as they have a nice paper in Nature a few weeks back showing how sequence conservation can be used to find enhancer elements.

They started with non-coding sequence elements that are either ultraconserved between mammalian species or showing conservation in Fugu. These elements were placed in a vector wit a naked promoter driving a reporter gene (lacZ) & microinjected into mouse eggs. Embryos were then stained at day 11.5.

Greater than 50% of the ultraconserved elements drove expression of the reporter gene, and further conservation in Fugu did not improve the finding of enhancers. But more than 1/4 of the Fugu-conserved sequences lacking mammalian ultra-conservation functioned as reporters. I do wish they had put in the frequency that random mammalian fragments will score positive in this assay; surely that sort of negative control data is out there somewhere. It's probably a very small fraction.

The articles, alas, require a Nature subscription -- but you can also browse the data at

One of their figures shows a variety of staining patterns driven from elements pulled from near the SALL1 gene. Various elements show very different staining patterns.

They also use 4 enhancers driving forebrain expression to find motifs, and in turn use those motifs to search the Fugu-Human element set. 17% of the hits act as forebrain-specific enhancers, whereas only 5% of the tested elements are forebrain enhancers. So even a with very small training set they were able to sigificantly enrich for the target expression pattern.

It will be interesting to see this approach continued, especially to annotate GUUFs (Genes of Utterly Unknown Function).

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