Sharing the SAGA

Abstract

Transcription initiation is a major regulatory step in eukaryotic gene expression. Co-activators establish transcriptionally competent promoter architectures and chromatin signatures to allow the formation of the pre-initiation complex (PIC), comprising RNA polymerase II (Pol II) and general transcription factors (GTFs). Many GTFs and co-activators are multisubunit complexes, in which individual components are organized into functional modules carrying specific activities. Recent advances in affinity purification and mass spectrometry analyses have revealed that these complexes often share functional modules, rather than containing unique components. This observation appears remarkably prevalent for chromatin-modifying and remodeling complexes. Here, we use the modular organization of the evolutionary conserved Spt-Ada-Gcn5 acetyltransferase (SAGA) complex as a paradigm to illustrate how co-activators share and combine a relatively limited set of functional tools. Many essential regulators of transcription initiation act as large, multiprotein complexes that are organized into structurally and functionally distinct modules. Recent advances in affinity purification and mass spectrometry analyses reveal that, rather than being unique to each complex, a functional module is frequently shared with at least one other regulatory complex. The well-conserved SAGA transcriptional co-activator represents an exemplary illustration of that phenomenon because all of its modules are shared with other complexes. Depending on the complex, these tools are used for either similar or distinct functions in gene expression. Sharing modules between distinct regulators might allow cells to coordinate their activities or, alternatively, to modulate the activity, substrate specificity, and localization of chromatin-modifying and remodeling enzymes.