Dynamic modules of the coactivator SAGA in eukaryotic transcription

Youngseo Cheon,Minhoo Kim,Harim Kim,Kyubin Park,Daeyoup Lee

doi:10.1038/s12276-020-0463-4

Abstract

SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved transcriptional coactivator that consists of four functionally independent modules. Its two distinct enzymatic activities, histone acetylation and deubiquitylation, establish specific epigenetic patterns on chromatin and thereby regulate gene expression. Whereas earlier studies emphasized the importance of SAGA in regulating global transcription, more recent reports have indicated that SAGA is involved in other aspects of gene expression and thus plays a more comprehensive role in regulating the overall process. Here, we discuss recent structural and functional studies of each SAGA module and compare the subunit compositions of SAGA with related complexes in yeast and metazoans. We discuss the regulatory role of the SAGA deubiquitylating module (DUBm) in mRNA surveillance and export, and in transcription initiation and elongation. The findings suggest that SAGA plays numerous roles in multiple stages of transcription. Further, we describe how SAGA is related to human disease. Overall, in this report, we illustrate the newly revealed understanding of SAGA in transcription regulation and disease implications for fine-tuning gene expression.

Highlights

Eukaryotic gene expression is extensively regulated, mostly at the transcription initiation step
SAGA was initially found to be important for both transcriptional activation and elongation, and more recent studies have shown that the complex is important for mRNA export, especially through the deubiquitylating module (DUBm)
It seems likely that the structural organization of its functional modules allows SAGA to execute comprehensive and dynamic regulation of gene expression

Summary

Official journal of the Korean Society for Biochemistry and Molecular Biology

Cheon et al Experimental & Molecular Medicine (2020) 52:991–1003 not appear to be involved in the p38 MAPK pathwaymediated acetylation of histones at sodium arseniteinduced promoters[11]. The ADA complex lacks an activator-targeting subunit, it is thought to be recruited to chromatin with relatively low specificity through the bromodomain of Gcn5p or the activatordomain-binding sites of Ada2p/Ada3p, whereby it helps maintain the global histone acetylation level. A recent study suggested that there may be an ADA-equivalent complex in Drosophila[33]; no homolog subunit of Ahc1p or Ahc2p has yet been identified in this model It is unclear whether this proposed complex can be considered homologous to the yeast ADA complex or whether it is a different form of the SAGA HAT module. Metazoans have two paralogous ADA2 proteins, ADA2a and ADA2b, which are specific to the ATAC HAT module and SAGA HAT module, respectively[37,38] ATAC1 modulates the histone H3 acetyltransferase activity of the ATAC complex[43]

HAT module Core module

Homo sapiens

TF binding module

The SAGA DUBm and transcription activation and elongation

Conclusion