tf

Nature 431, 99 - 104 (02 September 2004); doi:10.1038/nature02800

Transcriptional regulatory code of a eukaryotic genome

CHRISTOPHER T. HARBISON^1,2,*, D. BENJAMIN GORDON^1,*, TONG IHN LEE¹, NICOLA J. RINALDI^1,2, 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 KELLIS^1,3,4, P. ALEX ROLFE³, KEN T. TAKUSAGAWA³, ERIC S. LANDER^1,2,4, DAVID K. GIFFORD^3,4, ERNEST FRAENKEL^1,3 & RICHARD A. YOUNG^1,2,4

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
* These authors contributed equally to this work

Correspondence and requests for materials should be addressed to R.A.Y. (young@wi.mit.edu) or E.F. (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 expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, 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.