Genetic reconstruction of a functional transcriptional regulatory network

Although global analyses of transcription factor binding provide one view of potential transcriptional regulatory networks(1,2), regulation also occurs at levels distinct from transcription factor binding(3,4). Here, we use a genetic approach to identify targets of transcription factors in yeast and reconstruct a functional regulatory network. First, we profiled transcriptional responses in S. cerevisiae strains with individual deletions of 263 transcription factors. Then we used directed-weighted graph modeling and regulatory epistasis analysis to identify indirect regulatory relationships between these transcription factors, and from this we reconstructed a functional transcriptional regulatory network. The enrichment of promoter motifs and Gene Ontology annotations provide insight into the biological functions of the transcription factors.