Supplemental material for L. Omberg, J. R. Meyerson, K. Kobayashi, L. S. Drury, J. F. X. Diffley and O. Alter, "Global Effects of DNA Replication and DNA Replication Origin Activity on Eukaryotic Gene Expression," Molecular Systems Biology (MSB) 5, article 312 (October 2009); doi: 10.1038/msb.2009.70.
Press Release: B. Rische, "Mathematical Modeling Correctly Predicts Previously Unknown Biological Mechanism of Regulation," American Association for the Advancement of Science (AAAS) EurekAlert! (October 13, 2009).
Recommendation: M. Méchali, Faculty Opinions recommendation 1728974 (February 2010).
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Abstract:
This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher-order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, ∼88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3' ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation.

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Omberg_et_al_MSB_2009.pdf

A PDF format file of Supplementary information Sections, Figures and Tables, readable by Adobe Acrobat Reader.

Omberg_et_al_MSB_2009_Supplementary_Information.pdf

Tab-delimited text format files, readable by both Mathematica and Microsoft Excel.

Yeast mRNA Expression Data

• Dataset 1: UT_Microarrays.txt

Relative mRNA expression levels of 4771 probes of the University of Texas (UT) DNA microarrays that correspond to the K=4270 genes across 24 samples.

• Dataset 2: WU_Microarrays.txt

Relative mRNA expression levels of 8540 probes of the Washington University (WU) DNA microarrays that correspond to the K=4270 genes across 72 samples.

• Dataset 3: Averaged_Data_Tensor.txt

The averaged log₂ of the relative mRNA expression of the K=4270 genes across the L=12 time points and across the M=3 conditions of Mcm2-7 origin binding. The genes are sorted by their angular distances between the second and third HOSVD combinations (Supplementary information Section 2.6 and Dataset 6), which represent the unperturbed cell cycle expression oscillations (Figure 2 and Supplementary Figure 12). The angular distance of each gene is also listed.

Annotations of Yeast ARSs and Genes

• Dataset 4: ARS_Annotations.txt

Descriptions and genomic coordinates of the 325 confirmed ARSs in Saccharomyces cerevisiae from the Replication Origin Database (OriDB) by Nieduszynski et al.

• Dataset 5: Gene_Annotations.txt

Cell cycle annotations of the 4270 yeast genes from Spellman et al., DNA damage responses from Jelinsky and Samson, and descriptions and genomic coordinates from the Saccharomyces Genome Database (SGD) by Cherry et al.

Selected Eigenarrays and Superpositions of Eigenarrays

• Dataset 6: Eigenarrays.txt

The eigenarrays and superpositions of eigenarrays that define the global gene expression patterns of the seven significant and unique subtensors of the averaged data cuboid. The expression levels of the genes in the intersections of the fourth through seventh HOSVD combinations, as computed by using the corresponding eigenarrays, are also tabulated. The ten significant among the 1294 genes that are underexpressed in the fourth and overexpressed in the fifth and sixth combinations are enriched in histone genes. The 100 significant among the 1412 genes that are overexpressed in the fourth and underexpressed in the fifth and seventh combinations are enriched in genes with ARSs near their 3' ends.