| Until recently, the study of transcription and gene expression in general has been limited to a narrow set of genes and promoter sequences. These limitations have been overcome through the advent of genome sequencing projects and technological developments. The complete DNA sequence of the budding yeast Saccharomyces cerevisiae was completed in 1997. We used this information to construct a DNA microarray containing essentially every one of the 6,000 open reading frames present in the genome. The DNA microarray serves as a hybridization target against which fluorescently labeled nucleic acid samples may be applied. By labeling separate samples with differing fluorophores, this format permits the individual and simultaneous measurement of relative mRNA abundance levels for all genes in the genome. These tools were used to explore and observe genome-wide gene expression patterns for a variety of conditions. These include metabolic perturbations, induction of stress responses, genetic manipulations, drug treatments, and developmental progressions. These studies showed that metabolic flux could be inferred from expression patterns, targets of transcription factors could be directly revealed through overexpression or deletion of that factor, and importantly, that groups of coordinately regulated genes could be extracted from the data to reveal cis-acting sequences responsible for their expression. This technique was also applied to a limited set of human derived sequences, demonstrating the feasibility of observing genome wide expression patterns as it pertains to the study of cancer. These studies represent the first observations of whole genome gene expression, and reveal new insights into genomic regulation. |
