MODULES OF THE SAGA CHROMATIN-MODIFYING COMPLEX PLAY DISTINCT ROLES IN DROSOPHILA GENE EXPRESSION AND DEVELOPMENT

Abstract

Histone modifications are an important component of epigenetic control. Histone modifying enzymes are often integrated into large multi-subunit complexes. The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and if they have any SAGA independent functions. In this study, I took advantage of genetic approaches in Drosophila to remove the maternal contribution and investigated the requirement for the SAGA individual modules in early development. I found that perturbation of the HAT and the TAF module caused defects in oogenesis and a complete inability to form mature oocytes. By contrast, DUB activity was expendable during oogenesis, and at least some early zygotic genes were transcriptionally active. Nevertheless it was essential for normal cellularization in these early embryos, and their survival through embryogenesis. It was also essential for wild-type levels of transcription. I identified binding sites for several SAGA subunits genome wide in early embryos and found coincident binding at most sites. Notably, the DUB module bound to chromatin with other SAGA subunits even when it was not required for transcription of the associated genes. More interestingly, we identified sites in which DUB and TAF module subunits bound chromatin independent of the core SAGA modules, where it regulated transcription.