Scientists at the University of Virginia Health System have identified another step in the mysterious process of gene regulation -- what turns genes on or off, making them cause or suppress disease and other physical developments in humans. As reported in this week’s issue of the scientific journal Nature, a chemical group called ubiquitin has been shown to lie upstream of a switch that seems to control whether a gene is on or off. "Ubiquitin was first discovered on histones long ago, but before this study, we really did not know what it was doing in chromatin," said lead author and investigator Zu-Wen Sun, senior post-doctoral fellow in the Department of Biochemistry and Molecular Genetics at U.Va. Ubiquitin is one of manydistinct kinds of chemical "flags" that are known to be present on histone proteins.
Histones are protein building blocks around which the DNA is coiled much like a Slinky toy. Together, they form a structure called chromatin, where additional levels of gene regulation occur outside the DNA itself. One mechanism for regulating gene expression in the form of chromatin is through the addition or removal of chemical groups that are attached to the histone proteins. These histone proteins are nearly identical in most complex living organisms, from humans to yeast, which was used as a model in this study. They are highly decorated with different kinds of chemical groups including methyl- and acetyl- groups. Distinct patterns of these marks may operate together to form a ’histone code’ that, in turn, precedes and influences gene activities within the chromatin, according to studies published last year by C. David Allis, Byrd Professor of Biochemistry and Molecular Genetics at U.Va., who is co-author of the new study.
The four major types of histones each have a long "tail" which "wags" outside the surface of the chromatin fiber. Last year’s studies examined lysines at the fourth (K4) and ninth (K9) positions on the tail of one of the histones, H3, and revealed that when a chemical methyl group is added to these two positions, it turns genes on or off, acting much like a master control switch according to a histone code.
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