Dynamic modules of the coactivator SAGA in eukaryotic transcription

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

doi:10.1038/s12276-020-0463-4

Cited by 40 publications

(36 citation statements)

References 152 publications

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“…S5) that are associated with TSS (Zhao et al, 2011), and (iv) elevated occupancy of PfGCN5 (Fig. S5), the P. falciparum homolog of GCN5 protein (Bhowmick et al, 2020), which is a component of the SAGA transcription coactivator complex that acetylates histones at core promoters and enhancers (Cheon et al, 2020). Furthermore, C1 nucleotides are located mostly outside of protein-coding exons (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identifying transcript 5′ capped ends in Plasmodium falciparum

Shaw

Piriyapongsa

Kaewprommal

et al. 2021

PeerJ

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Background The genome of the human malaria parasite Plasmodium falciparum is poorly annotated, in particular, the 5′ capped ends of its mRNA transcripts. New approaches are needed to fully catalog P. falciparum transcripts for understanding gene function and regulation in this organism. Methods We developed a transcriptomic method based on next-generation sequencing of complementary DNA (cDNA) enriched for full-length fragments using eIF4E, a 5′ cap-binding protein, and an unenriched control. DNA sequencing adapter was added after enrichment of full-length cDNA using two different ligation protocols. From the mapped sequence reads, enrichment scores were calculated for all transcribed nucleotides and used to calculate P-values of 5′ capped nucleotide enrichment. Sensitivity and accuracy were increased by combining P-values from replicate experiments. Data were obtained for P. falciparum ring, trophozoite and schizont stages of intra-erythrocytic development. Results 5′ capped nucleotide signals were mapped to 17,961 non-overlapping P. falciparum genomic intervals. Analysis of the dominant 5′ capped nucleotide in these genomic intervals revealed the presence of two groups with distinctive epigenetic features and sequence patterns. A total of 4,512 transcripts were annotated as 5′ capped based on the correspondence of 5′ end with 5′ capped nucleotide annotated from full-length cDNA data. Discussion The presence of two groups of 5′ capped nucleotides suggests that alternative mechanisms may exist for producing 5′ capped transcript ends in P. falciparum. The 5′ capped transcripts that are antisense, outside of, or partially overlapping coding regions may be important regulators of gene function in P. falciparum.

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Section: Discussionmentioning

confidence: 99%

Identifying transcript 5′ capped ends in Plasmodium falciparum

Shaw

Piriyapongsa

Kaewprommal

et al. 2021

PeerJ

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“…The SAGA co-activator is a paradigm of a multisubunit complex with distinct functions (see recent reviews in [19,[33][34][35][36][37]). Although identi ed more than twenty years ago, there remain many open questions about its function and modularity.…”

Section: Discussionmentioning

confidence: 99%

SAGA-CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity

Nuño-Cabanes

García-Molinero

Martín-Expósito

et al. 2020

Preprint

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Background: Histone H2B deubiquitination is performed by numerous deubiquitinases in eukaryotic cells including Ubp8, the catalytic subunit of the tetrameric deubiquitination module (DUBm: Ubp8; Sus1; Sgf11; Sgf73) of the Spt-Ada-Gcn5 acetyltransferase (SAGA). Ubp8 is linked to the rest of SAGA through Sgf73 and is activated by the adaptors Sus1 and Sgf11. It is unknown if DUBm/Ubp8 might also work in a SAGA-independent manner. Results: Here we report that a tetrameric DUBm is assembled independently of the SAGA-CORE components SPT7, ADA1 and SPT20. In the absence of SPT7, i.e. independent of the SAGA complex, Ubp8 and Sus1 are poorly recruited to SAGA-dependent genes and to chromatin. Notably, cells lacking Spt7 or Ada1, but not Spt20, show lower levels of nuclear Ubp8 than wild type cells, suggesting a possible role for SAGA-CORE subunits in Ubp8 localization. Last, deletion of SPT7 leads to defects in Ubp8 deubiquitinase activity in in vivo and in vitroassays. Conclusions: Collectively, our studies show that the DUBm tetrameric structure can form without a complete intact SAGA-CORE complex and that it includes full length Sgf73. However, subunits of this SAGA-CORE influence DUBm association with chromatin, its localization and its activity.

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“…The next major discovery was that yeast SAGA contains not only HAT activity, but also histone deubiquitinase (DUB) activity. H2B lysine 123 undergoes ubiquitination, which serves as a transient signal that orchestrates a diverse set of events during transcription (Shilatifard 2006;Fleming et al 2008;Cheon et al 2020). Four subunits have been identified in yeast SAGA that are required to cleave monoubiquitin from H2B.…”

Section: The Saga Complex Not Only Contains Histone Acetylation But Also Ubiquitin Protease Activitymentioning

confidence: 99%

The SAGA chromatin-modifying complex: the sum of its parts is greater than the whole

Soffers

Workman

2020

Genes Dev.

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There are many large protein complexes involved in transcription in a chromatin context. However, recent studies on the SAGA coactivator complex are generating new paradigms for how the components of these complexes function, both independently and in concert. This review highlights the initial discovery of the canonical SAGA complex 23 years ago, our evolving understanding of its modular structure and the relevance of its modular nature for its coactivator function in gene regulation.

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Dynamic modules of the coactivator SAGA in eukaryotic transcription

Cited by 40 publications

References 152 publications

Identifying transcript 5′ capped ends in Plasmodium falciparum

Identifying transcript 5′ capped ends in Plasmodium falciparum

SAGA-CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity

The SAGA chromatin-modifying complex: the sum of its parts is greater than the whole

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