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Genome-wide binding map of the histone deacetylase Rpd3 in yeast

Nature Genetics volume 31, pages 248–254 (2002)Cite this article

Abstract

We describe the genome-wide distribution of the histone deacetylase and repressor Rpd3 and its associated proteins Ume1 and Ume6 in Saccharomyces cerevisiae. Using a new cross-linking protocol, we found that Rpd3 binds upstream of many individual genes and upstream of members of gene classes with similar functions in anabolic processes. In addition, Rpd3 is preferentially associated with promoters that direct high transcriptional activity. We also found that Rpd3 was absent from large sub-telomeric domains. We show by co-immunoprecipitation and by the high similarity of their binding maps that Ume1 interacts with Rpd3. In contrast, despite the known role of Ume6 in Rpd3 recruitment, only a limited number of the genes targeted by Rpd3 are also enriched for (or targeted by) Ume6. This suggests that Rpd3 is brought to many promoters by alternative recruiters, some of which may bind the putative cis-regulatory DNA elements that we have identified in sets of Rpd3 target genes. Finally, we show that comparing the genome-wide pattern of Rpd3 binding with gene expression and histone acetylation in the rpd3Δ mutant strain reveals new sites of Rpd3 function.

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Figure 1: Rpd3 binds to both promoter and global sites.
Figure 2: Rpd3 binds preferentially to promoters that direct high transcriptional activity.
Figure 3: Ume1 is a newly discovered member of the Rpd3 complex in yeast.
Figure 4: Rpd3 is excluded from telomeric and sub-telomeric regions.
Figure 5: Rpd3 binding is complementary to acetylation and expression arrays.

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Acknowledgements

We are grateful to P.O. Brown for providing the primer sets for the intergenic arrays and to the laboratory of S. Nelson for use of their microarray scanner. We also thank T. Tsukiyama for providing yeast strains and plasmids for PCR-based tagging, I. Xenarios for help with data analysis, J.S. Wu for help with co-immunoprecipitation experiments and members of the Grunstein laboratory for discussions throughout this work. S.K.K. is a Howard Hughes Medical Institute Physician Postdoctoral Fellow. D.R. is a recipient of fellowships from the Swiss National Science Foundation and the Roche Research Foundation. This work was supported by Public Health Service grants from the National Institutes of Health (to M.G.).

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Authors and Affiliations

  1. Department of Biological Chemistry, University of California School of Medicine, Los Angeles, 90095, California, USA

    Siavash K. Kurdistani, Daniel Robyr & Michael Grunstein

  2. Department of Pathology and Laboratory Medicine, University of California School of Medicine, Los Angeles, 90095, California, USA

    Siavash K. Kurdistani

  3. Department of Molecular Biology, Lewis Thomas Laboratories, Princeton University, Princeton, New Jersey, USA

    Saeed Tavazoie

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Correspondence to Michael Grunstein.

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Kurdistani, S., Robyr, D., Tavazoie, S. et al. Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nat Genet 31, 248–254 (2002). https://doi.org/10.1038/ng907

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