Supporting Information

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Fig. 9. MA plots showing differential expression induced by suberoylanilide hydroxamic acid (SAHA) and depsipeptide over time as measured by microarray analysis. Microarray data were background corrected and normalized as described in Materials and Methods. Postnormalized MA plots show the distribution of intensity values and log-ratios, where the intensity log-ratio M = log₂ (R / G) vs. the mean log-intensity A = log2Ö RG is plotted. R, background corrected red; G, background corrected green intensity. Each plot displays the results from one microarray, and each plotted point represents a single spot on the array. The plots show a steadily increasing range of log-ratios over the time course, indicating increasing differential expression. Data shown are the first series of six time points for SAHA (A) and depsipeptide (B) and are representative of the three replicate experiments. Lucidea scorecard control spots (Amersham Pharmacia) are highlighted on the plots. Ratio controls are spiked in to be 3-fold and 10-fold up-regulated (U03 and U10, red points) or 3-fold or 10-fold down-regulated (D03 and D10, green points), whereas dynamic range spots (DR, dark blue points) should show no differential expression over a range of intensities. These controls help to calibrate the observed log-ratios. Other controls are negative controls (NC and Reserved, brown and yellow points), positive controls spotted with genomic DNA (PC, light blue points), and various housekeeping genes (HG, pink points). All of the control spots behave as expected, confirming the quality of the microarray printing, labeling, and hybridizations.

Fig. 10. Gene expression profiles induced by SAHA and depsipeptide in CEM cells. CEM cells were treated with 2.5 m M SAHA, 0.1 m M depsipeptide, or vehicle control, harvested at the indicated times, and gene expression was analyzed as described in Materials and Methods. Genes that were differentially regulated by at least 1.5-fold from time 0 h to at least one later time point in response to SAHA (n = 2,205) (A) and depsipeptide (n = 2,466) (B) are shown. Up-regulated genes are depicted in red, down-regulated genes are depicted in green, and each line corresponds to a single gene.

Fig. 11. Functional clustering of SAHA- and depsipeptide-regulated cell proliferation-related genes. Expression profiles of all commonly regulated cell proliferation-related genes. Genes were hierarchically clustered based on standard correlation coefficients. A complete list of genes in this cluster can be found in Table 3.

Fig. 12. Functional clustering of SAHA- and depsipeptide-regulated apoptosis-related genes. Expression profiles of all commonly regulated apoptosis-related genes. Genes were hierarchically clustered based on standard correlation coefficients.

Fig. 13. Hierarchical cluster analysis of gene expression profiles induced by SAHA in cycling and arrested cells. Genes selected as differentially expressed by SAHA in cycling and/or arrested cells based on a 1.5-fold up- or down-regulation from time 0 h to at least one later time point were clustered based on standard correlation coefficients by using expression ratios in cycling cells (Left), and this gene order was retained for the arrested cells (Right).

Fig. 14. Expression profiles of genes specifically regulated by SAHA in cycling and arrested cells. Genes identified as specifically regulated by SAHA in cycling (n = 107) or arrested (n = 303) cells are shown, with their corresponding expression in response to SAHA in the other cell population. Up-regulated genes are depicted in red, down-regulated genes are depicted in green, and each line corresponds to a single gene.