Transcriptional regulatory code of a eukaryotic genome

Transcriptional regulatory code of a eukaryotic genome

2004 September 2; 431(7004): 99–104 | Christopher T. Harbison, D. Benjamin Gordon, Tong Ihn Lee, Nicola J. Rinaldi, Kenzie D. Macisaac, Timothy W. Danford, Nancy M. Hannett, Jean-Bosco Tagne, David B. Reynolds, Jane Yoo, Ezra G. Jennings, Julia Zeitlinger, Dmitry K. Pokholok, Manolis Kellis, P. Alex Rolfe, Ken T. Takusagawa, Eric S. Lander, David K. Gifford, Ernest Fraenkel, Richard A. Young
The authors have constructed an initial map of the transcriptional regulatory code in yeast by identifying sequence elements bound by transcriptional regulators under various conditions and conserved among *Saccharomyces* species. They used genome-wide location analysis to determine the genomic occupancy of 203 DNA-binding transcriptional regulators in rich media and in at least one of 12 other environmental conditions. The study identified 11,000 unique interactions between regulators and promoter regions at high confidence. By merging information from genome-wide location data, phylogenetically conserved sequences, and prior knowledge, they discovered 68,279 DNA sequence motifs for 147 regulators. The distribution of binding sites revealed constraints on their organization in yeast promoters, with most sites located between 100 and 500 bp upstream of the protein-coding sequence. The authors also observed four common patterns of regulator binding behavior: 'condition-invariant,' 'condition-enabled,' 'condition-expanded,' and 'condition-altered,' each with distinct mechanisms of action. This work provides a framework for modeling the mechanisms contributing to global gene expression and suggests that similar approaches can be used to map regulatory sequences in higher eukaryotes.The authors have constructed an initial map of the transcriptional regulatory code in yeast by identifying sequence elements bound by transcriptional regulators under various conditions and conserved among *Saccharomyces* species. They used genome-wide location analysis to determine the genomic occupancy of 203 DNA-binding transcriptional regulators in rich media and in at least one of 12 other environmental conditions. The study identified 11,000 unique interactions between regulators and promoter regions at high confidence. By merging information from genome-wide location data, phylogenetically conserved sequences, and prior knowledge, they discovered 68,279 DNA sequence motifs for 147 regulators. The distribution of binding sites revealed constraints on their organization in yeast promoters, with most sites located between 100 and 500 bp upstream of the protein-coding sequence. The authors also observed four common patterns of regulator binding behavior: 'condition-invariant,' 'condition-enabled,' 'condition-expanded,' and 'condition-altered,' each with distinct mechanisms of action. This work provides a framework for modeling the mechanisms contributing to global gene expression and suggests that similar approaches can be used to map regulatory sequences in higher eukaryotes.
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