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'Noisy' genes can have big impact

of the gene regulating its expression. In this scheme, if there were no noise, every cell would appear the same mix of blue and yellow color under the microscope. However, if any noise crept in, it would produce a variation in colors among the cells. This color variation could then be measured to determine the amount of noise that was present. This method eliminated any influence of external environmental factors or variables such as differences in cell type, since the two genes were operating inside the same cell.

After using this technique to study the function of various promoters, the scientists concluded that noise did, indeed, affect gene expression in the yeast cells. They also found that different promoters produced different amounts of noise.

Based on their studies, Raser and O'Shea believe they have identified the source of a major portion of the random noise they observed. "Our experiments suggest that for the promoters we studied, a major source of noise is the act of preparing the promoter DNA, the regulatory region, to be competent for transcription," said O'Shea. This preparation, she said, involves "remodeling" the protective structure, called the nucleosome, which enfolds the regulatory region of the gene so that the transcription machinery can access it. "And the step that is generating noise is this act of removing the nucleosomes, in order to allow access of the transcription machinery and the regulatory proteins," she said.

Remodeling is particularly slow, O'Shea said, and subject to significant probabilistic variation. This variation would likely have an affect on the amount of mRNA produced for each marker-tagged gene and thus the level of a given protein in the cell -- affecting its color.

According to O'Shea, randomness in gene express could have important evolutionary and biological implications, both advantageous for cells and deleterious. For example, mutations in genes could change their "noisiness" independent of
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
27-May-2004


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