Sort Experiments

Finally, we are interested in finding other microarray experiments that may be relevant to gene regulation by Ume6p. Therefore, we click on the "Sort Experiments" tab and are presented with the list of all PSAMs similar to the display from the "Browse PSAMs" tab. We scroll down to UME6_H2O2Hi and click on the affinity logo. We are then given a list of all expression samples sorted by the absolute t-value of the correlation between their expression values and the predicted promoter occupancies for UME6_H2O2Hi. Of course, we see a number of the experiments from the dataset that we just explored. We can investigate the experimental design of any of the samples with which we are unfamiliar by clicking on the "GEO" link next to the sample title, which takes us to the NCBI GEO website [1]. After following several of these links we find that many of these other experiments are independent studies on sporulation, as could be expected. However, there are other experimental designs among the top scoring experiment samples. Of special interest is a segregant from a cross between a lab strain and wild strain of S. cerevisiae, suggesting that there is polymorphism that affects Ume6p regulation [15]. Also, of great interest are a series of experiments that examined expression in a variety of strains that had mutations eliminating one or more of four acetylation sites on the N-terminal tail of histone H4 [16]. Ume6p is known to regulate expression of its target genes by recruiting Sin3p and Rpd3p to hypoacetylate histones H3 and H4 [17]. If the lysines that get acetylated are absent from a histone, it may affect the ability of Ume6p to regulate gene expression. By examining the sorted list of experiments, we see that the expression of Ume6p targets are significantly altered (E-value <= 10^-3) if at least three of the lysines are mutated. Dion et al. [16] report that the mutations of the lysines of histone H4 has a largely non-specific effect on gene expression with over a thousand genes affected. However, due to the strong correlation between expression under histone H4 lysine mutations and predicted Ume6p binding, being regulated by Ume6p must make genes particularly sensitive to alterations in histone acetylation.