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Epigenetics shows that a gene being turned on or off can change the hereditary phenotype of both plants and animals for generations without harming their DNA. If the DNA isn’t harmed, then future generations may be able to adapt to changing situations.
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Epigenetics can lock in particular patterns of gene expression in plants and animals, says Purdue biochemist Joe Ogas. This selection process allows organisms to pass on genes that will give their offspring the best chance to survive in their environment. (Photo by Tom Campbell) |
“A plant wants as much potential success for its progeny as possible,” says Joe Ogas, biochemistry professor, who works with a mustard-cousin research plant, Arabidopsis. “Imagine that over the course of evolution a plant has come to realize that it’s experienced a certain environment and that its offspring are likely to experience that environment as well. Epigenetics regulation offers the potential to turn off or turn on certain sets of genes in anticipation of the offspring being successful in that environment.
“Similarly with animals—epigenetics can lock in a particular pattern of gene expression. Selection is a powerful driving force in evolution, and it’s had millennia to identify best-case strategies for an organism to successfully pass genes on to the next generation.“
Ogas studies a gene called “PKL“ involved in rearranging histones so that the enzymes similar to those Briggs works with can modify the histones. Methyl groups aren’t the only biochemical mechanisms that cause epigenetic changes. Acetylation and ubiquitylation are also biochemical mechanisms that can add or subtract small molecules to turn genes on or off. Interest by national and international research groups and funding sources is gaining momentum in the quest to determine how these processes work.
The National Institutes of Health and the National Science Foundation (NSF) have earmarked federal funding specifically for studying the epigenome. Purdue biochemist Ann Kirchmaier recently received a nearly $500,000 NSF grant to probe the mystery of how deacetylation silences—permanently turns off—genes in cells and how epigenetic change is inherited.
“The heritable feature of epigenetic gene regulation necessitates that cells tightly control if, when and where silencing will occur,” Kirchmaier says. “If the wrong genes are permanently turned on or off, it can lead to developmental defects, cancer and other catastrophic disorders.”
Finding ways to stop improper flicking of genetic switches is spawning a new class of drugs, and scientists are striving for even more. Researchers now are experimenting with epigenetics to program cell function for use in repairing specific injuries and diseases.
Stopping the mistakes
University of Wisconsin and Kyoto University scientists last year made a skin cell regress so that it was no longer a skin cell. The cell didn’t know where it belonged yet; it had been transformed into an undifferentiated cell, or stem cell, the same type of cell that causes controversy if it comes from an embryo.
Understanding how to trigger the on/off genetic switch may allow scientists to remove some of the genetic programming that tells a cell to change from an undifferentiated embryo cell to a cell designed for a specific function, such as bone or muscle.
“If we can understand epigenetics, then we can understand how to reverse gene expression from on to off or vice versa. We already know that as a cell progresses from a stem cell to a differentiated state there are a large number of epigenetic changes,” Ogas says. “The more we understand the changes, the more we’ll be able to direct cells to particular outcomes.”
Understanding how to use epigenetics-based genetic reprogramming could help treat people with many disorders, including children like those Lossie hugged at Prader-Willi conferences and Angelman syndrome clinics.
“These kids are just really special,” says Lossie, whose graduate school advisors were involved with patients with the disorders. “Being able to see the kids, and talk with the kids and the parents, and knowing that someday we might be making a difference kept me going in graduate school. It’s at the forefront for me today: How can we make a difference?”
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