UCSF

Metazoan transcriptional regulation is governed by combinatorial control, in which distinct multifactor regulatory complexes composed of various combinations of factors assemble at different genomic sites. The vast number of unique combinations enables, in principle, a virtually inexhaustible roster of specific transcription patterns. However, it is unclear what directs combinatorial assembly of regulatory complexes that may have a hundred or more different proteins and what distinguishes different complexes in both composition and function. To begin addressing this problem, we probed pairs of factors that reside together in subsets of functionally distinguishable complexes. We tested whether we could use this "paired analysis" of the occupancy and activities of just two factors to functionally classify large complexes. Specifically, we analyzed the composition, activities, and determinants of multifactor complexes containing the glucocorticoid receptor or NFkappaB and the coregulator Brm at differentially regulated genes. Our results showcase the complexity of combinatorial regulation and open pathways to further analysis and understanding.