Modularity of the transcriptional response of protein complexes in yeast

A comprehensive study is performed on the condition-dependent expression of genes coding for the components of hand curated multi-protein complexes of the yeast Saccharomyces cerevisiae, in order to identify coherent transcriptional modules within these complexes. Such modules are defined as groups of genes within complexes whose expression profiles under a common set of experimental conditions allow us to discriminate them from random sets of genes. Our analysis reveals that complexes such as the cytoplasmic ribosome, the proteasome and the respiration chain complexes previously characterized as stable or permanent represent transcriptional modules that are coherently up or down-regulated in many different conditions. Overall however, some level of coherent expression is detected only in 71 out of the total of 113 complexes with at least five different protein components that could be reliably analyzed. Of these, 26 behave as coherently expressed transcriptional modules encompassing all the components of the complex. In another 15, at least half of the components make up such modules and in ten, few or no modules are detected. In an additional 20 complexes coherent expression is detected, but in too few conditions to enable reliable module detection. Interestingly, the transcriptional modules, when detected, often correspond to one or more known sub-complexes with specific functions. Furthermore, detected modules are generally consistent with transcriptional modules identified on the basis of predicted cis-regulatory sequence motifs. Also, groups of genes shared between complexes that carry out related functions tend to be part of overlapping transcriptional modules identified in these complexes. Together these findings suggest that transcriptional modules may represent basic functional and evolutionary building blocs of protein complexes. (c) 2006 Elsevier Ltd. All rights reserved.