Three-pronged genomic analysis reveals yeast cell-type regulation circuitry

摘要

Institute of Molecular Biology, University of Oregon, Eugene, OR 97403-1229 The phenotypic and physiological potential of a cell is determined by its transcription program, which, in turn, is determined by the array of transcription factors present in the cell. A sophisticated and detailed understanding of the role of a particular transcription factor requires that all of its target genes be identified. This task is a daunting one, but it has become feasible with the availability of complete genome sequences, coupled with genome-wide analytical methods such as transcription profiling and chromatin immunoprecipitation (ChIP) assays. In a recent study, Harbison et al. (1) used ChIP analysis, together with predicted sequence-recognition motifs, to determine the genomic occupancy of 203 DNA-binding transcription regulators in yeast. Because of the scope of that study, the question of whether all of the targets of a particular transcription regulator function in a particular physiological setting were identified was left unanswered. In a recent issue of PNAS, Galgoczy et al. (2) focus on a specific biological question with the goal of identifying the complete set of target genes for the transcription regulators that determine cell type in the budding yeast Saccharomyces cerevisiae. Cell-type specification in yeast has been studied intensely in a number of laboratories over the last 20 years, and the information gained from those studies served as a touchstone for the current work; that is, certain targets could be anticipated. However, there is ample room for surprise. Some target genes may have eluded discovery, and it is conceivable that the cell-type regulators also make connections to other physiological processes. Indeed, both possibilities are re- alized in the current study. In their work, Galgoczy et al. (2) used ChIP analysis, as had Harbison et al. (1), but, in addition, they used transcription profiling and phylogenetic comparisons. The application of all three approaches resulted in "overdetermination" of the target gene sets for the yeast cell-type regulators, giving one confidence that the complete sets have been identified.