| The advances in microarray technology that enabled parallel reactions on a massive scale have caused genomic research to evolve into systems biology. Researchers can now begin organizing the genes of an organism into what will be extremely complex networks that carry out the biological tasks of life. This daunting undertaking can be approached from an understanding of the mechanisms of transcriptional regulation. The work described herein introduces methods for elucidating the regulation of eukaryotic genes. The computational devices that lead to such results, and an understanding of the underlying mechanisms of transcriptional regulation in lower organisms, can ultimately provide insights to transcriptional regulation in humans, assisting in the efficient selection of drug targets.; In order to determine the combinations of transcription factors that regulate a gene and characterize the binding site motif to which a regulating transcription factor binds, gene expression profiles, protein-DNA binding profiles, and intergenic region sequences are analyzed to fully investigate the chronologically linked events of promoter recognition, factor-promoter binding and gene transcription. Individually, these events provide evidence of regulation but lack the certainty that merits investment on resource-intensive biological experimentation. However, taken together as the basis of our combinatoric and stochastic models, they lead to strong hypotheses about the required combinations of inducers and repressors of gene transcription, the characterization of binding site motif sequences, and maximum likelihood estimations of the abundance requirements on the transcripts themselves. Transcriptional regulation models are presented for several key genes in the Saccharomyces cerevisiae pheromone response pathway. |
