Letter

Transcriptional regulatory code of a eukaryotic genome

Received:
Accepted:
Published online:

Abstract

DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression1. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation2,3,4,5,6, but this information alone does not reveal if or when transcriptional regulators occupy these binding sites. We have constructed an initial map of yeast's transcriptional regulatory code by identifying the sequence elements that are bound by regulators under various conditions and that are conserved among Saccharomyces species. The organization of regulatory elements in promoters and the environment-dependent use of these elements by regulators are discussed. We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast's transcriptional regulators.

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Acknowledgements

We thank T. Ideker and S. McCuine for help in selecting regulators to study in environmental conditions; E. Herbolsheimer, G. Bell, R. Latek and F. Lewitter for computational assistance; and E. McReynolds for technical assistance. E.F. is a Whitehead Fellow and was funded in part by Pfizer. D.B.G. was supported by a NIH/NIGMS NRSA award. This work was supported by an NIH grant.

Author information

Author notes

    • Christopher T. Harbison
    •  & D. Benjamin Gordon

    These authors contributed equally to this work

Affiliations

  1. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA

    • Christopher T. Harbison
    • , D. Benjamin Gordon
    • , Tong Ihn Lee
    • , Nicola J. Rinaldi
    • , Nancy M. Hannett
    • , Jean-Bosco Tagne
    • , David B. Reynolds
    • , Jane Yoo
    • , Ezra G. Jennings
    • , Julia Zeitlinger
    • , Dmitry K. Pokholok
    • , Manolis Kellis
    • , Eric S. Lander
    • , Ernest Fraenkel
    •  & Richard A. Young
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Christopher T. Harbison
    • , Nicola J. Rinaldi
    • , Eric S. Lander
    •  & Richard A. Young
  3. MIT Computer Science and Artificial Intelligence Laboratory, 32 Vassar Street, Cambridge, Massachusetts 02139, USA

    • Kenzie D. Macisaac
    • , Timothy W. Danford
    • , Manolis Kellis
    • , P. Alex Rolfe
    • , Ken T. Takusagawa
    • , David K. Gifford
    •  & Ernest Fraenkel
  4. Broad Institute, One Kendall Square, Building 300, Cambridge, Massachusetts 02139, USA

    • Manolis Kellis
    • , Eric S. Lander
    • , David K. Gifford
    •  & Richard A. Young

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Competing interests

Some authors have filed a patent application covering aspects of this work and are pursuing commercialization.

Corresponding authors

Correspondence to Ernest Fraenkel or Richard A. Young.

Supplementary information

PDF files

  1. 1.

    Supplementary Figures 1-5

    These figures show distributions of regulator binding, an overview of our motif-discover process, an example of in vitro regulator binding, the effect of environmental conditions on genomic binding, and a change in the quality of Gcn4 binding sites in different environmental conditions.

Word documents

  1. 1.

    Supplementary Tables 1-8

    These tables list the regulators and environmental conditions examined, a comparison of discovered motifs to literature, the compendium of regulator specificities, characterizations of regulator architectures, a classification of regulator binding behaviours, and motif scoring metrics.

  2. 2.

    Supplementary Methods

    This file contains additional information about all aspects of experimental procedures used.

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