If you learned in high school biology that chromosomes are made up of genes that are used as a template to make proteins, you’re half right — or, in the case of maize, five percent right. In reality, only a small fraction of the DNA that makes up corn chromosomes is “coding” — active duty — DNA; the rest is silent — and by and large needs to stay that way, or it could cause big trouble by making proteins (or protein-like molecules) that do more harm than good. How does the cell know which genetic material to transcribe, and which to ignore?
That question has been dogging plant geneticist Nathan Springer for a long time. Now it appears he may be onto an answer. Springer and colleagues reported their findings in the Proceedings of the National Academy of Sciences in November.
Springer studies epigenetics — heritable changes cells make to their genetic material without changing the actual DNA sequence. He knew that previous studies in a simple plant, Arabidopsis, suggested that a process that adds a specific tag, mCHH, to some regions of DNA plays a role in labeling noncoding DNA as “hands off” to the transcription machinery looking for protein-making templates. He also knew that in Arabidopsis and many other plants, the noncoding DNA tends to be lumped together in certain regions of chromosomes, making it relatively easy for the protein-making machinery to distinguish the true templates.
But Springer studies the genetics of maize, which has a far bigger and more complex genome than arabidopsis, with coding and noncoding DNA interspersed throughout rather than isolated. If mCHH is what tells the cell which DNA is noncoding, there should be lots more mCHH in maize than in Arabidopsis. But, in reality, there is far less. What, he wondered, is that all about?
To find out, Springer enlisted a team to gather massive amounts of data about how coding and noncoding DNA and mCHH are distributed in the maize genome. Compiling information about the location of mCHH in DNA from various tissues and maize plants, the team discovered that mCHH clusters, creating “islands” that appear next to almost half the maize genes and are especially likely to occur near active genes. They also discovered that mutations that eliminate a cell’s ability to create mCHH islands don’t appear to affect the activity of nearby genes. Putting the pieces together, Springer and colleagues concluded that, in maize, mCHH islands create a sort of fence that makes noncoding DNA off limits to protein-making machinery on the prowl for genes to decode.
The research improves understanding of both the function of epigenetic structures and the regulation of DNA transcription. But Springer points out it could have some important practical applications as well for researchers working to meet growing global needs for food and other plant-based resources through genetic engineering. “When we drop a transgene into a genome, we don’t know who the neighbors are,” he says. Knowing the cues cells use to identify which DNA to transcribe and which to ignore can help researchers strategically insert new genes in a way that increases the likelihood they’ll actually get put to work.
— Mary Hoff / December 2015