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Review
. 2020 Jul;52(7):991-1003.
doi: 10.1038/s12276-020-0463-4. Epub 2020 Jul 3.

Dynamic modules of the coactivator SAGA in eukaryotic transcription

Youngseo Cheon #  1 , Harim Kim #  1 , Kyubin Park  1 , Minhoo Kim  2 , Daeyoup Lee  3
Affiliations
Review

Dynamic modules of the coactivator SAGA in eukaryotic transcription

Youngseo Cheon et al. Exp Mol Med. 2020 Jul.

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Schematic diagram showing the modular organization of the SAGA complex.
For the sake of simplicity, each subunit is labeled with the name used in S. cerevisiae. The schematic diagram shows the major functions of each module and presents recent structural data obtained from yeast,,. Subunits belonging to each module are colored similarly: red, HAT module; blue, core module; green, TF-binding module; and yellow, DUB module. Subunits having a histone octamer-like fold in the core module are depicted as half circles that form circles with their corresponding partners: Taf6-Taf9; Ada1-Taf12; Spt7-Taf10; and Spt3, which has two octamer-like folds. The dotted circle near Spt3 and Spt8 indicates the TBP-binding site, where TBP is recruited at the transcription initiation step.
Fig. 2
Fig. 2. SAGA regulates transcription to fine-tune gene expression.
Subunits that are major in each step are colored; otherwise, they are uncolored. a SAGA promotes an open chromatin structure through its HAT activity, which can be allosterically regulated by the proteasome to favor transcription initiation,. When this occurs, Bre1/Rad6-dependent H2Bub1 triggers the methylation of histone H3 by Set1, yielding TSS-associated histone modifications that act as markers to recruit downstream effectors that facilitate transcription initiation. b Deubiquitylation of ubiquitylated H2B is mediated by DUBm and is necessary for the recruitment of Ctk1, which phosphorylates Ser2 of RNAPII CTD and allows the release of paused RNAPII. For productive elongation, the nucleosome barrier must be overcome. Histone chaperones (FACT and Spt6) and chromatin remodelers may be essential in this process and may cooperatively regulate the transition from initiation to transcription elongation. c The Rpt2p-Sgf73p interaction leads to the separation of DUBm, and the separated Sgf73 contributes to cotranscriptional mRNP surveillance and the mRNA export pathway,. Sus1, which is a subunit of both DUBm and TREX-2, may mediate the targeting of genes to nuclear pore complexes (NPCs).
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References

    1. Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu. Rev. Biochem. 1998;67:545–579. - PubMed
    1. Carrozza MJ, Utley RT, Workman JL, Cote J. The diverse functions of histone acetyltransferase complexes. Trends Genet. 2003;19:321–329. - PubMed
    1. Brownell JE, et al. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996;84:843–851. - PubMed
    1. Grant PA, et al. Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes Dev. 1997;11:1640–1650. - PubMed
    1. Martinez E, Kundu TK, Fu J, Roeder RG. A human SPT3-TAFII31-GCN5-L acetylase complex distinct from transcription factor IID. J. Biol. Chem. 1998;273:23781–23785. - PubMed

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