Penn State researchers find that protein changes can control gene functions

A Penn State-led research team has found that changes to proteins called histones, which are associated with DNA, can control whether or not a gene is allowed to function. The changes may be important in maintaining the genes' "expression potential" so that future cells behave as their parent cells did. The discovery, which may have implications for the study of diseases such as cancer, will be published in a print edition of the journal Proceedings of the National Academy of Sciences. The research was led by Lu Bai, an assistant professor of biochemistry, molecular biology, and physics at Penn State University, in collaboration with David Stillman at the University of Utah.

Bai explained that gene expression -- the process by which certain genes are regulated or turned "on" or "off" -- is one of the most fundamental processes in the life of any biological cell. Different programs of gene expression -- even when cells have the same DNA -- can lead to different cellular behavior and function. For example, even though a human muscle cell and a human nerve cell have identical DNA, they behave and function very differently. "Gene expression tends to vary from cell to cell," Bai said. "Misregulation may happen in a small fraction of cells, and these cells may cause disease later on. Therefore it is important to study gene regulation at the single-cell level."

Using a fluorescent video of cell division, Bai and her team were able to observe how a gene called HO was expressed in single yeast cells over multiple cell divisions. Normally, the expression of HO allows budding yeast to change sex -- from "male" to "female" and vice versa. "Interestingly, HO expression -- and thus sex change -- is supposed to occur only in 'mother' cells but not the newly budded 'daughter' cells," Bai explained. After observing the video, team members found that HO was expressed in 98 percent of the mother cells but also in 3 percent of the daughter cells. "The vast majority of both the mother cells and the daughter cells responded as they were supposed to," Bai said. "But, in a small percentage of the cells, the gene regulation went wrong."

The pressing question for Bai's team then was, why did the HO gene regulation fail in a small population of cells -- in 2 percent of the mother cells and 3 percent of the daughter cells? She discovered that the answer seems to lie in histones, a major protein complex associated with DNA. "We found that changes in histone configurations affect the fraction of cells in which the HO expression was misregulated. In addition, we found that, in some conditions, the HO expression can 'remember' itself: If HO is turned on in one cell, it is more likely to be turned on in its progeny cells. We showed that this short-term memory of the HO expression seems to be inherited through histone modifications," Bai said. She added that further study of gene expression, specifically at the level of individual cells, can have important implications for disease research.

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Comments

  1. Long LifeProject Long LifeProject Canada says:

    The info here is too sketchy to determine if the aberration of misregulation was a function of diet or chemicals (natural or induced by the likes of Monsanto) measured in parts per trillion, or any other reason.

    • Alexander Grobman Alexander Grobman Peru says:

      The expression of each of the 30,000 genes of maize or the over 22,000 genes of humans is dependent onregulatory regions in the ADN, on the effect of external factors such as microRNA, proteins or epigenetic factors. The insertion of a transgen on a plant planned to express a useful trait in the right place in the organism is a feat of genetic engineering. Detailed studiesand biosafety evaluations and monitoring are conducted in order to insure that a single nitroduced transgenie is not subject  to the many "natural errors" which do take place on thousands of natural genes.... and the evidence is that it has been successful.

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