In the search to determine what controls how genes are expressed, an increasing number of studies are pointing to the fine print.

A new study out of UCLA and the Salk Institute for Biological Studies adds to that fine print by providing a comprehensive map the entire genome of a common laboratory plant, highlighting areas where DNA methylation may have taken place.

DNA methylation is an “epigenetic process”: it affects gene expression, but does not alter the sequence of bases that make up the genetic code. Methylation adds a methyl group to cytosine, one of the four DNA bases, and can silence genes by blocking their transcription into RNA. Because methylations can be inherited during DNA replication, in gene expression, they are just as important as any changes to the base sequence.

The new research on Arabidopsis thaliana — a flowering plant of that is considered the mouse of laboratory research plants—offers the first genome-wide analysis of methylation for any plant or animal.

“Now anyone can simply get on a browser and see the methylation status of their favorite gene,” said Steve Jacobsen, a plant biologist at UCLA and co-author of the study.

The entire genome of Arabidopsis thaliana consists of about 26,000 expressed genes, or about 120 million bases. The researchers determined where the DNA was methylated and compared that to microarrays that revealed whether the genes were turned on.

The scientists found that the location of a methylation influenced its effects. For instance, methylation on the body of the gene corresponded to higher levels of expression, rather than the expected lower levels. But when methylation occurred in the gene’s promoter region—an area adjacent to the body of the gene and where transcription begins—it was more likely to silence the gene.

More than a third of expressed genes had methylation in their transcribed regions, whereas only five percent had them in the promoter regions.

The team also found that methylation silences transposons, so-called “jumping genes” that can move around in the genome and cause wide-ranging genetic problems. 

The scientists also studied mutant plants that were unable to methylate DNA. In these plants, they discovered hundreds of genes that showed higher levels of activity than in normal plants. This suggests that these genes might be controlled by methylation and are effectively silenced in many normal plants.

“There is a lot of DNA variation,” said Joseph Ecker, a plant biologist at the Salk Institute for Biological Studies and co-author of the study. “But we don’t really know on a genome-wide scale the degree of epigenetic scale.”

Rob Martienssen, a plant geneticist at Cold Spring Harbor Laboratory, said methylation profiles are useful for crop plants and genetically modified organisms (GMOs).

“Methylation profiling of GMO plants would be a good way to ensure there have been no unintended epigenetic changes during the modification process, which could negatively impact crop performance,” he said.

Originally published September 13, 2006

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