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Promoter-specific binding of Rap1 revealed by genome-wide maps of protein–DNA association

Nature Genetics volume 28, pages 327–334 (2001)Cite this article

An Erratum to this article was published on 01 September 2001

Abstract

We determined the distribution of repressor-activator protein 1 (Rap1) and the accessory silencing proteins Sir2, Sir3 and Sir4 in vivo on the entire yeast genome, at a resolution of 2 kb. Rap1 is central to the cellular economy during rapid growth, targeting 294 loci, about 5% of yeast genes, and participating in the activation of 37% of all RNA polymerase II initiation events in exponentially growing cells. Although the DNA sequence recognized by Rap1 is found in both coding and intergenic sequences, the binding of Rap1 to the genome was highly specific to intergenic regions with the potential to act as promoters. This global phenomenon, which may be a general characteristic of sequence-specific transcriptional factors, indicates the existence of a genome-wide molecular mechanism for marking promoter regions.

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Figure 1: Determination of Rap1 targets.
Figure 2: Map of the interaction between Rap1 and the S. cerevisiae genome.
Figure 3: Rap1 binds preferentially to potential promoters
Figure 4: Rap1 binds to the promoters of heavily transcribed genes.

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Acknowledgements

We thank V. Iyer for initiating work on the intergenic yeast array, and other members of the Brown and Botstein labs for advice and technical support. We thank D. Brutlag and J. Liu for advice in developing BioProspector, J. Derisi for software that maps the IP data, and J. Rine for yeast strains. This work was supported by a grant from the National Human Genome Research Institute and by the Howard Hughes Medical Institute. P.O.B. is an associate investigator of the Howard Hughes Medical Institute, and the Helen Hay Whitney Foundation supports J.D.L.

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Authors and Affiliations

  1. Department of Biochemistry, Stanford University, Stanford, 94305-5428, California, USA

    Jason D. Lieb & Patrick O. Brown

  2. Stanford Medical Informatics, Stanford University, Stanford, 94305-5428, California, USA

    Xiaole Liu

  3. Department of Genetics, Stanford University, Stanford, 94305-5428, California, USA

    David Botstein

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  1. Jason D. Lieb
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  2. Xiaole Liu
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Corresponding author

Correspondence to Patrick O. Brown.

Supplementary information

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Web Figure H:

Download the .cdt, .gtr, and .pcl files corresponding to the cluster of gene expression profiles for the genes downstream of intergenic fragments selected by the Rap1p IP. These files must be loaded into Treeview to view the clusters. Instructions for using Treeview (http://rana.lbl.gov/EisenSoftware.htm) can be found in the Treview Manual.

Web Figure H: .cdt, .gtr, and .pcl files (ZIP 702 KB)

Web Figure H: Treeview Manual (PDF 291 KB)

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Web Table I

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Lieb, J., Liu, X., Botstein, D. et al. Promoter-specific binding of Rap1 revealed by genome-wide maps of protein–DNA association. Nat Genet 28, 327–334 (2001). https://doi.org/10.1038/ng569

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