Since his postdoctoral surprise, Jacobsen and colleagues have been systematically deconstructing DNA methylation. They used the hypermethylated SUPERMAN mutants (called clark kent mutants) to screen for genes that maintain proper patterns of DNA methylation. Using this trick, Jacobsen and colleagues cloned three genes—CHROMOMETHYLASE3, KRYPTONITE, and ARGONAUTE4—that further clarify methylation mechanics and the interaction of methylated DNA with modified histones (proteins that help wrap up the DNA into tightly packed chromosomes) as well as with small RNA molecules that target methylation. Last summer, Jacobsen's team described how plants use RNA interference (RNAi), or RNA silencing, to target specific genes for DNA methylation.

Now, Jacobsen's team is working to pinpoint every instance of DNA methylation in the Arabidopsis genome. The lab's initial efforts were reported in the September 1, 2006, online edition of the journal Cell. With this model organism map, Jacobsen says, scientists will be able to find similar activity in the more complex human genome. “Although not identical, DNA methylation in plants and humans is sufficiently similar that we can glean useful information,” he says.

Scientists also have sidled up to the potting bench to analyze regulatory RNA. Over the past decade, regulatory RNA has won recognition as a major coordinator of gene expression in cells of various species. Indeed, the petunia, streaked in different colors, provided some of the first evidence that regulatory RNA can silence pigment genes during development.

Today, HHMI investigator David Bartel, a biologist at the Massachusetts Institute of Technology, is studying plant regulatory RNA for insight into animal development. Bartel's lab studies in particular how microRNAs (miRNAs) silence genes. In 2002, having found many miRNAs in animals, Bartel wondered whether these molecules might also exist in diverse species—namely, plants. He contacted an inside resource for Arabidopsis plants: his sister, Bonnie Bartel, a plant biologist at Rice University who became an HHMI professor this year. Teaming up, the sibling duo set about analyzing mustard plants for regulatory RNAs. They hit the jackpot.

“At the time, only three known targets of animal miRNA existed,” says David Bartel. “When we mapped just one miRNA (miR171) to the Arabidopsis genome, we turned up three different targets. That's when it got exciting. Soon we had about 50 confidently identified targets and could begin to consider the broad functions of these regulatory RNAs.” Bartel, who had never worked with plants before, promptly hired several scientists to study plant miRNAs full-time.

The team has identified miRNAs in Arabidopsis that, for example, regulate embryonic and organ development, and analogous targets in animal models. The team also honed lab techniques for plants, such as high-throughput sequencing methods, before adapting them to animal studies. Interestingly, Bartel notes that although miRNAs in plants and animals have the same silencing effect, their mechanisms usually differ considerably. He speculates that miRNAs evolved at least twice, once in early plants and again in early animals. Today, Arabidopsis has at least 100 known miRNA genes, while humans have more than 400.

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