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A genome-wide analysis in Saccharomyces cerevisiae demonstrates the influence of chromatin modifiers on transcription


Chromatin structure is important in transcription regulation. Many factors influencing chromatin structure have been identified, but the transcriptional programs in which they participate are still poorly understood. Chromatin modifiers participate in transcriptional control together with DNA-bound transcription factors. High-throughput experimental methods allow the genome-wide identification of binding sites for transcription factors as well as quantification of gene expression under various environmental and genetic conditions. We have developed a new methodology that uses the vast amount of available data to dissect the contribution of chromatin structure to transcription. We measure and characterize the dependence of transcription factor function on specific chromatin modifiers. We apply our methodology to S. cerevisiae, using a compendium of 170 gene expression profiles of strains defective for chromatin modifiers, taken from 26 different studies. Our method succeeds in identifying known intricate genetic interactions between chromatin modifiers and transcription factors and uncovers many previously unknown genetic interactions, giving the first genome-wide picture of the contribution of chromatin structure to transcription in a eukaryote.

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Figure 1: A model for chromatin modifier-mediated transcription.
Figure 2: The chromatin modifier gene expression compendium.
Figure 3: Distribution of expression values for the Ume6 cohort in various chromatin modifier knockout experiments.
Figure 4: Overlap in altered cohort genes.
Figure 5: Distribution of expression values for the Yap6 cohort in various chromatin modifier knockout experiments.


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We thank A. Tanay for guidance and ideas and all the members of the Kupiec and Shamir laboratories for discussions and encouragement. This work was supported in part by grants from the Israel Science Foundation to M.K. and R.S. and a grant from the Israeli Ministry of Science and Technology to M.K.

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Correspondence to Martin Kupiec.

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Supplementary information

Supplementary Fig. 1

Complete hierarchical clustering solution for all K-S scores. (PDF 178 kb)

Supplementary Fig. 2

Yap6_(ypd) and Skn7_(h2o2lo) activated genes. (PDF 76 kb)

Supplementary Table 1

The publications from which the gene expression data were obtained. (PDF 37 kb)

Supplementary Table 2

All KS scores. (PDF 1844 kb)

Supplementary Table 3

Unique pairs of TFs and CMs. (XLS 39 kb)

Supplementary Table 4

TATA-containing cohorts. (PDF 19 kb)

Supplementary Note (PDF 78 kb)

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Steinfeld, I., Shamir, R. & Kupiec, M. A genome-wide analysis in Saccharomyces cerevisiae demonstrates the influence of chromatin modifiers on transcription. Nat Genet 39, 303–309 (2007).

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