Letters to Nature

Nature 431, 99-104 (2 September 2004) | doi:10.1038/nature02800; Received 11 March 2004; Accepted 1 July 2004

Transcriptional regulatory code of a eukaryotic genome

Christopher T. Harbison1,2,5, D. Benjamin Gordon1,5, Tong Ihn Lee1, Nicola J. Rinaldi1,2, Kenzie D. Macisaac3, Timothy W. Danford3, Nancy M. Hannett1, Jean-Bosco Tagne1, David B. Reynolds1, Jane Yoo1, Ezra G. Jennings1, Julia Zeitlinger1, Dmitry K. Pokholok1, Manolis Kellis1,3,4, P. Alex Rolfe3, Ken T. Takusagawa3, Eric S. Lander1,2,4, David K. Gifford3,4, Ernest Fraenkel1,3 & Richard A. Young1,2,4

  1. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  3. MIT Computer Science and Artificial Intelligence Laboratory, 32 Vassar Street, Cambridge, Massachusetts 02139, USA
  4. Broad Institute, One Kendall Square, Building 300, Cambridge, Massachusetts 02139, USA
  5. These authors contributed equally to this work

Correspondence to: Ernest Fraenkel1,3Richard A. Young1,2,4 Email: young@wi.mit.edu
Email: efraenkel@wi.mit.edu
ArrayExpress number E-WMIT-10 has been given for microarray data.

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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