SAGA Is a General Cofactor for RNA Polymerase II Transcription

The SAGA coactivator complex facilitates transcription initiation through chromatin-modifying activities and interaction with TBP. SAGA was suggested to regulate the expression of about 10% of yeast genes, leading to the longstanding distinction of SAGA-dominated from TFIID-dominated genes, depending on the complex used to recruit TBP to promoters. We reassessed the genome-wide localization of SAGA by using Prior studies suggested that the coactivator complexes SAGA and TFIID promote RNA polymerase II transcription at discrete set of genes with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA. We also find that the acetyltransferase Gcn5 and Spt3 (a TBP interacting subunit) synergize to promote global transcription and that Spt3 functions to stimulate TBP recruitment at all tested genes Our data demonstrate that SAGA acts as a general cofactor required for essentially all RNA polymerase II transcription and is not consistent with the previous classification of SAGA and TFIID-dominated genes.