Sumoylation controls the timing of Tup1-mediated transcriptional deactivation

Ng, Chong Han; Akhter, Akhi; Yurko, Nathan; Burgener, Justin M.; Rosonina, Emanuel; Manley, James L.

doi:10.1038/ncomms7610

Cited by 25 publications

(22 citation statements)

References 51 publications

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“…In another, somewhat related study, sumoylation of the Tup1 transcriptional repressor on K229 and K270 was found to promote binding of Tup1 to the ARG1 promoter . The authors proposed that Tup1 sumoylation mediates the subsequent transcriptional deactivation that is required to downregulate ARG1 expression after the initial burst of transcription.…”

Section: Sumo As a Transcriptional Repressor: The Dogmamentioning

confidence: 97%

SUMO‐regulated transcription: Challenging the dogma

Chymkowitch

Enserink

2015

BioEssays

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The small ubiquitin-like modifier SUMO regulates many aspects of cellular physiology to maintain cell homeostasis, both under normal conditions and during cell stress. Components of the transcriptional apparatus and chromatin are among the most prominent SUMO substrates. The prevailing view is that SUMO serves to repress transcription. However, as we will discuss in this review, this model needs to be refined, because recent studies have revealed that SUMO can also have profound positive effects on transcription.

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Section: Sumo As a Transcriptional Repressor: The Dogmamentioning

confidence: 97%

SUMO‐regulated transcription: Challenging the dogma

Chymkowitch

Enserink

2015

BioEssays

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“…In a genome-wide study, SUMO was found to be enriched at genes encoding tRNA and ribosomal protein (RP) genes, and sumoylation of the Rap1 transcriptional regulator promotes recruitment of the basal transcription machinery to these genes (Chymkowitch et al, 2015a). Interestingly, SUMO plays an important role not only in transcriptional activation by the Gcn4 transcription factor but also in subsequent transcriptional deactivation through a combination of SUMO-dependent clearance of Gcn4 and stabilization of Tup1 corepressor binding at promoters (Ng et al, 2015). The yeast SUMO proteases also can modulate transcription.…”

Section: Introductionmentioning

confidence: 99%

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Ryu

Wilson-Eisele

et al. 2019

The EMBO Journal

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Many eukaryotic proteins are regulated by modification with the ubiquitin‐like protein small ubiquitin‐like modifier (SUMO). This linkage is reversed by SUMO proteases, of which there are two in Saccharomyces cerevisiae, Ulp1 and Ulp2. SUMO‐protein conjugation regulates transcription, but the roles of SUMO proteases in transcription remain unclear. We report that Ulp2 is recruited to transcriptionally active genes to control local polysumoylation. Mutant ulp2 cells show impaired association of RNA polymerase II (RNAPII) with, and diminished expression of, constitutively active genes and the inducible CUP1 gene. Ulp2 loss sensitizes cells to 6‐azauracil, a hallmark of transcriptional elongation defects. We also describe a novel chromatin regulatory mechanism whereby histone‐H2B ubiquitylation stimulates histone sumoylation, which in turn appears to inhibit nucleosome association of the Ctk1 kinase. Ctk1 phosphorylates serine‐2 (S2) in the RNAPII C‐terminal domain (CTD) and promotes transcript elongation. Removal of both ubiquitin and SUMO from histones is needed to overcome the impediment to S2 phosphorylation. These results suggest sequential ubiquitin‐histone and SUMO‐histone modifications recruit Ulp2, which removes polySUMO chains and promotes RNAPII transcription elongation.

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“…Xenopus Groucho is SUMOylated at multiple sites, and SUMOylation enhances its corepressor activity (Ahn et al, 2009). Similarly, the yeast Groucho ortholog Tup1 has recently been shown to be SUMOylated, and although mutation of its SUMO sites does not affect initial recruitment to target promoters, it does affect its ability to remain on the promoters, suggesting SUMO stabilizes the corepressor complex (Ng et al, 2015). Interestingly, Tup1 interaction partners histone H3, Cti6, Gcn5, Gal11, and Cyc8 also become SUMOylated under similar conditions as Tup1, and SUMO may generally hold together transcriptional repressor complexes in the same manner that SUMO protein functions to hold together DNA repair systems and PML nuclear bodies (Psakhye and Jentsch, 2012; Shen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Function of the C. elegans T-box factor TBX-2 depends on interaction with the UNC-37/Groucho corepressor

Huber

Crum

Okkema

2016

Developmental Biology

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T-box transcription factors are important regulators of development in all animals, and altered expression of T-box factors has been identified in an increasing number of diseases and cancers. Despite these important roles, the mechanism of T-box factor activity is not well understood. We have previously shown that the C. elegans Tbx2 subfamily member TBX-2 functions as a transcriptional repressor to specify ABa-derived pharyngeal muscle, and that this function depends on SUMOylation. Here we show that TBX-2 function also depends on interaction with the Groucho-family corepressor UNC-37. TBX-2 interacts with UNC-37 in yeast two-hybrid assays via a highly conserved engrailed homology 1 (eh1) motif located near the TBX-2 C-terminus. Reducing unc-37 phenocopies tbx-2 mutants, resulting in a specific loss of anterior ABa-derived pharyngeal muscles and derepression of the tbx-2 promoter. Moreover, double mutants containing hypomorphic alleles of unc-37 and tbx-2 exhibit enhanced phenotypes, providing strong genetic evidence that unc-37 and tbx-2 share common functions in vivo. To test whether interaction with UNC-37 is necessary for TBX-2 activity, we developed a transgene rescue assay using a tbx-2 containing fosmid and found that mutating the tbx-2 eh1 motif reduced rescue of a tbx-2 null mutant. These results indicate that TBX-2 function in vivo depends on interaction with UNC-37. As many T-box factors contain eh1 motifs, we suggest that interaction with Groucho-family corepressors is a common mechanism contributing to their activity.

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Sumoylation controls the timing of Tup1-mediated transcriptional deactivation

Cited by 25 publications

References 51 publications

SUMO‐regulated transcription: Challenging the dogma

SUMO‐regulated transcription: Challenging the dogma

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Function of the C. elegans T-box factor TBX-2 depends on interaction with the UNC-37/Groucho corepressor

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