A study published in *Nature* (2004) identifies the transcriptional regulatory code of the yeast genome. The research team, led by Christopher T. Harbison and Richard A. Young, used genome-wide location analysis to determine the genomic occupancy of 203 DNA-binding transcriptional regulators under various environmental conditions. They identified 11,000 unique interactions between regulators and promoter regions with high confidence (P ≤ 0.001). By combining genome-wide location data, phylogenetically conserved sequences, and prior knowledge, they discovered 68,279 DNA sequence motifs for 147 regulators. These motifs were used to determine the most likely specificity for each regulator, revealing significant insights into transcriptional regulation. The study mapped the regulatory code on the yeast genome, identifying 3,353 interactions within 1,296 promoter regions. The results show that transcriptional regulators function at short distances along linear DNA, reducing the potential for inappropriate activation of nearby genes. The study also identified four patterns of environment-specific regulator binding: condition-invariant, condition-enabled, condition-expanded, and condition-altered. These patterns highlight how regulators respond to different environmental conditions, with some regulators showing consistent binding across environments, while others show changes in binding behavior depending on the environment. The study provides a framework for modeling the mechanisms that contribute to global gene expression in yeast. It also suggests that the approaches used to map regulatory sequences in yeast can be applied to higher eukaryotes. The research highlights the importance of combining regulator binding data with sequence conservation data to understand the regulatory code of the genome. The findings have significant implications for understanding gene regulation in eukaryotic organisms.A study published in *Nature* (2004) identifies the transcriptional regulatory code of the yeast genome. The research team, led by Christopher T. Harbison and Richard A. Young, used genome-wide location analysis to determine the genomic occupancy of 203 DNA-binding transcriptional regulators under various environmental conditions. They identified 11,000 unique interactions between regulators and promoter regions with high confidence (P ≤ 0.001). By combining genome-wide location data, phylogenetically conserved sequences, and prior knowledge, they discovered 68,279 DNA sequence motifs for 147 regulators. These motifs were used to determine the most likely specificity for each regulator, revealing significant insights into transcriptional regulation. The study mapped the regulatory code on the yeast genome, identifying 3,353 interactions within 1,296 promoter regions. The results show that transcriptional regulators function at short distances along linear DNA, reducing the potential for inappropriate activation of nearby genes. The study also identified four patterns of environment-specific regulator binding: condition-invariant, condition-enabled, condition-expanded, and condition-altered. These patterns highlight how regulators respond to different environmental conditions, with some regulators showing consistent binding across environments, while others show changes in binding behavior depending on the environment. The study provides a framework for modeling the mechanisms that contribute to global gene expression in yeast. It also suggests that the approaches used to map regulatory sequences in yeast can be applied to higher eukaryotes. The research highlights the importance of combining regulator binding data with sequence conservation data to understand the regulatory code of the genome. The findings have significant implications for understanding gene regulation in eukaryotic organisms.