A study from the University of the Free State (UFS) on how the change in the packaging of DNA with cell development influenced the expression of genes, will be published in this week’s early edition of the prestigious international, peer-reviewed science journal, the Proceeding of the National Academy of Sciences of the USA (PNAS).
The PNAS journal has an impact factor of 10, which means that studies published in the journal are, on average, referred to by ten other scientific studies in a two year period. The South African Journal of Science, by comparison, has an impact factor of 0.7.
The UFS study, funded by the Wellcome Trust and the National Research Foundation (NRF), looked at how the change in the packaging of DNA with cell development influenced the expression of genes. It is very relevant to research on stem cells, an area of medicine that studies the possible use of undifferentiated cells to replace damaged tissue.
Prof. Hugh Patterton, of the Department of Microbial, Biochemical and Food Biotechnology at the UFS, who led the study, said: "We are extremely proud of this study. It was conceived in South Africa, it was performed in South Africa, the data were analysed in South Africa, and it was published from South Africa."
When a gene is expressed, the information encoded in the gene is used to manufacture a specific protein. In eukaryotes, which include humans, there is approximately 1m of DNA, containing the genes, in every cell. This length of DNA has to fit into a cell nucleus with a diameter of only about 10 micrometer. In order to fit the DNA into such a small volume, eukaryotic cells wrap their DNA onto successive protein balls, termed nucleosomes. Strings of nucleosomes, resembling a bead of pearls, is folded into a helix to form a chromatin fiber. The study from the UFS investigated how the binding of a specific protein, termed a linker histone, that binds to the length of DNA between nucleosomes, influenced the formation of the chromatin fiber and also the activity of genes.
"We found that the linker histone bound to chromatin in yeast, which we use as a model eukaryote, under conditions where virtually all the genes in the organism were inactive. It was widely believed that the binding of the linker histone caused the inactivation of genes. We studied the relationship between the amount of linker histone bound in the vicinity of each gene and the expression of that gene for all the genes in yeast, using genomic techniques. We made the surprising discovery that even through the linker histone preferentially bound to genes under conditions where the genes were shut off, this inactivation of genes was not caused by the binding of the linker histone and folding of the chromatin,” said Prof. Patterton.
He said: “Instead our data strongly suggested that the observed anti-correlation was due to the movement of enzymes along the DNA molecule, involved in processing the information in genes for the eventual manufacture of proteins. This movement of enzymes displaced the linker histones from the DNA. This finding now requires a rethink on aspects of how packaging of DNA influences gene activity."
Prof. Patterton said that his research group, using the Facility for Genomics and Proteomics as well as the Bioinformatics Node at the UFS, was currently busy with follow-up studies to understand how other proteins in nucleosomes affected the activities of genes, as well as with projects to understand how chemicals found in red wine and in green tea extended lifespan. "We are certainly having a marvelous time trying to understand the fundamental mechanisms of life, and the UFS is an exciting place to be if one was interested in studying life at the level of molecules," he said.
Media Release
Issued by: Lacea Loader
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Tel: 051 401 2584
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18 September 2008