Abstract
Regulation of eukaryotic gene expression depends on groups of related proteins acting at the levels of chromatin organization, transcriptional initiation, RNA processing, and nuclear transport. However, a unified understanding of how these different levels of transcriptional control interact has been lacking. Here, we combine genome-wide protein-DNA binding data from multiple sources to infer the connections between functional groups of regulators in Saccharomyces cerevisiae. Our resulting transcriptional network uncovers novel biological relationships; supporting experiments confirm new associations between actively transcribed genes and Sir2 and Esc1, two proteins normally linked to silencing chromatin. Analysis of the regulatory network also reveals an elegant architecture for transcriptional control. Using communication theory, we show that most protein regulators prefer to form modules within their functional class, whereas essential proteins maintain the sparse connections between different classes. Moreover, we provide evidence that communication between different regulatory groups improves the robustness and adaptivity of the cell.