Role of the SWIRM Domain in Regulating the HAT Module of the SAGA Complex

Abstract

The SAGA (Spt‐Ada‐Gcn5 acetyltransferase) co‐activator complex regulates most yeast genes and both acetylates and deubiquitinates chromatin. SAGA contains the acetyltransferase, Gcn5, which is found in the four‐protein subcomplex known as the HAT module. On its own, Gcn5 is unable to acetylate nucleosomal and chromatin substrates. To acetylate chromatin, Gcn5 depends on two of the other HAT subunits, Ada2 and Ada3, and its activity is further enhanced by the presence of the last subunit, Sgf29. While recent cryo‐EM structures have resolved much of the SAGA complex, the structure of the HAT module could not be resolved due to poorly defined density. HAT module subunit, Ada2, contains a SWIRM domain, which is found in other chromatin modifying enzymes but whose function varies based on context. Here we show that the yeast S. cerevisiae SWIRM domain is required for incorporation of the HAT module into the SAGA complex. This study investigates how loss of the SWIRM domain affects the HAT module’s function in yeast and its ability to acetylate and bind nucleosomes. The insights from this work will aid in understanding why the SWIRM chromatin reader domain is important for histone acetylation, a vital step in making chromatin accessible to transcription.