Genome-wide analysis of the context-dependence of regulatory networks

One of the earliest benefits of the complete genome sequences of major model organisms was the development of hybridization-array technology - DNA microarrays, or chips - which has enabled the mRNA levels for every gene in a genome to be monitored simultaneously [1]. This gives a picture of the transcriptome, the complete set of genes being expressed in a given cell or organism under a particular set of conditions. It should be possible to exploit such transcriptome data together with information on regulatory interactions to determine how cells regulate their gene-expression programs. But most efforts to map genome-scale transcription regulatory networks either have produced a network relevant only to one growth condition [2] or have included all previously described regulatory interactions, thus representing the total regulatory potential of the genome [3]. These static representations miss the importance of environmental transitions and ignore the time-dependence of regulatory interactions. In other words, the context-dependence that is intrinsic to functional genomics studies [4] has been lost or ignored.A complete and dynamic description of gene regulation should enable us to answer a number of fundamental questions. What is the mechanistic basis of context-dependent regulatory interactions? How can a relatively small number of regulators respond to a huge variety of conditions? Can we identify 'design principles' in the architecture of transcriptional regulatory networks? What are the main functional differences between the underlying regulatory networks of the endogenous (developmental) and exogenous (sensory) gene-expression programs?Two approaches have recently been applied to mapping the gene regulatory networks of the budding yeast Saccharomyces cerevisiae in different physiological contexts. In the first, Harbison et al. [5] determined which sites on yeast chromosomes were occupied by which transcription factors under a number of environmental conditions