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Reformatting the genome
Unlocking the natural history of DNA
As every biology major knows, “Phenotype = genotype plus environment.” We can’t do much about our genotype (or at least until Craig Venter has his way), but what about modification of gene expression?
The addition of a methyl group to our genes (DNA methylation) is a potent way to silence expression. Aberrations in gene expression due to methylation/demethylation have been well characterized in various cancers. Also, as the stem cell field has shown, tight control of gene expression occurs in early development and clearly governs cell fate.
Christian Popp and colleagues at the Babraham Insitute and UCLA have shown (in their recent Nature paper) that the enzyme Activation-Induced cytidine Deaminase (AID) has a profound effect on DNA methylation.
In mice that lacked the AID gene (AID-/- ), day 13.5 mouse embryos had substantial DNA methylation across their genomes (i.e. gene expression OFF) in contrast to wild type (AID+/+) mice who showed a substantial lack of DNA methylation (i.e. gene expression ON).
The authors concluded that this mechanism is active across the entire genome and may be the critical method used to govern gene expression in early mammalian development. AID essentially acts as a “hard drive defragmenter” for the genome and prevents epigenetic mutations from being passed on to future generations.
Now that we know the mechanism whereby gene expression is controlled in development (AID enzyme), we can combine that knowledge with insights from stem cell biology. This could serve as the foundation for changing cell behavior in a variety of tissues, especially if they need to be “reset” to remove a damaging trait.
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John McCulloch @ MaRS
John provides assistance to life sciences entrepreneurs in business strategy, management, intellectual property, financing and licensing.
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