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Transcriptional regulatory code of a eukaryotic genome.

ABSTRACT: 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.

SUBMITTER: Harbison CT

PROVIDER: S-EPMC3006441 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

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Transcriptional regulatory code of a eukaryotic genome.

Harbison Christopher T CT Gordon D Benjamin DB Lee Tong Ihn TI Rinaldi Nicola J NJ Macisaac Kenzie D KD Danford Timothy W TW Hannett Nancy M NM Tagne Jean-Bosco JB Reynolds David B DB Yoo Jane J Jennings Ezra G EG Zeitlinger Julia J Pokholok Dmitry K DK Kellis Manolis M Rolfe P Alex PA Takusagawa Ken T KT Lander Eric S ES Gifford David K DK Fraenkel Ernest E Young Richard A RA

Nature 20040901 7004

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 ide ...[more]

PMID: 15343339

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Project description:Regulation of gene expression via specific cis-regulatory promoter elements has evolved in cellular organisms as a major adaptive mechanism to respond to environmental change. Assuming a simple model of transcriptional regulation, genes that are differentially expressed in response to a large number of different external stimuli should harbor more distinct regulatory elements in their upstream regions than do genes that only respond to few environmental challenges. We tested this hypothesis in Arabidopsis thaliana using the compendium of gene expression profiling data available in AtGenExpress and known cis-element motifs mapped to upstream gene promoter regions and studied the relation of the observed breadth of differential gene expression response with several fundamental genome architectural properties. We observed highly significant positive correlations between the density of cis-elements in upstream regions and the number of conditions in which a gene was differentially regulated. The correlation was most pronounced in regions immediately upstream of the transcription start sites. Multistimuli response genes were observed to be associated with significantly longer upstream intergenic regions, retain more paralogs in the Arabidopsis genome, are shorter, have fewer introns, and are more likely to contain TATA-box motifs in their promoters. In abiotic stress time series data, multistimuli response genes were found to be overrepresented among early-responding genes. Genes involved in the regulation of transcription, stress response, and signaling processes were observed to possess the greatest regulatory capacity. Our results suggest that greater gene expression regulatory complexity appears to be encoded by an increased density of cis-regulatory elements and provide further evidence for an evolutionary adaptation of the regulatory code at the genomic layout level. Larger intergenic spaces preceding multistimuli response genes may have evolved to allow greater regulatory gene expression potential.

Dataset Information

Transcriptional regulatory code of a eukaryotic genome.

Publications

Transcriptional regulatory code of a eukaryotic genome.

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