Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes (original) (raw)
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PLOS Genetics, 2021
Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters to facilitate RNAPII recruitment and transcription initiation. To explore how sumoylation can regulate transcription genome-wide, we performed SUMO ChIP-seq in yeast and found, in agreement with others, that most chromatin-associated sumoylated proteins are detected at genes encoding tRNAs and ribosomal proteins (RPGs). However, we also detected 147 robust SUMO peaks at promoters of non-ribosomal protein-coding genes (non-RPGs), indicating that sumoylation also regulates this gene class. Importantly, SUMO peaks at non-RPGs align specifically with binding sites of GTFs, but not other promoter-associated proteins, indicating that it is GTFs specifically that are sumoylated there. Predomina...
Regulation of transcription factors by sumoylation
Transcription, 2017
Transcription factors (TFs) are among the most frequently detected targets of sumoylation, and effects of the modification have been studied for about 200 individual TFs to date. TF sumoylation is most often associated with reduced target gene expression, which can be mediated by enhanced interactions with corepressors or by interference with protein modifications that promote transcription. However, recent studies show that sumoylation also regulates gene expression by controlling the levels of TFs that are associated with chromatin. SUMO can mediate this by modulating TF DNA-binding activity, promoting clearance of TFs from chromatin, or indirectly, by influencing TF abundance or localization.
Journal of Biological Chemistry
Ribosome biogenesis is critical for proliferating cells and requires the coordinated activities of three eukaryotic RNA polymerases. We recently showed that the small ubiquitin-like modifier (SUMO) system controls the global level of RNA polymerase II (Pol II)-controlled transcription in mammalian cells by regulating cyclin-dependent kinase 9 (CDK9) activity. Here, we present evidence that the SUMO system also plays a critical role in the control of Pol I transcription. Using an siRNA-based knockdown approach, we found that multiple SUMO E3 ligases of the protein inhibitor of activated STAT (PIAS) family are involved in SUMO-mediated repression of rDNA gene transcription. We demonstrate that endogenous SUMO represses rDNA transcription primarily by repressing upstream-binding factor (UBF) and proto-oncogene c-Myc (c-Myc) expression and that ectopic overexpression of SUMO-associated enzymes additionally represses rDNA transcription via c-Myc SUMOylation and its subsequent degradation. The results of our study reveal a critical role of SUMOylation in the control of rDNA transcription, uncover the underlying mechanisms involved, and indicate that the SUMO system coordinates Pol I-and Pol II-mediated transcription in mammalian cells.
SUMO and transcriptional regulation
Seminars in Cell & Developmental Biology, 2004
The small ubiquitin-like modifier (SUMO) is covalently attached to lysine residues in target proteins and in doing so changes the properties of the modified protein. Here we examine the role of SUMO modification in transcriptional regulation. SUMO addition to components of the transcriptional apparatus does not have a common consequence as it can both activate and repress transcription. In most cases, however, SUMO modification of transcription factors leads to repression and various models to explain this, ranging from retention in nuclear bodies to recruitment of histone deacetylases are discussed. (R.T. Hay). modified by specific SUMO types and SUMO-2/-3 are thought to be conjugated to protein targets in response to a variety of cellular stress events .
Defining the SUMO-modified Proteome by Multiple Approaches in Saccharomyces cerevisiae*
Journal of Biological Chemistry, 2005
SUMO, or Smt3 in Saccharomyces cerevisiae, is a ubiquitin-like protein that is post-translationally attached to multiple proteins in vivo. Many of these substrate modifications are cell cycle-regulated, and SUMO conjugation is essential for viability in most eukaryotes. However, only a limited number of SUMO-modified proteins have been definitively identified to date, and this has hampered study of the mechanisms by which SUMO ligation regulates specific cellular pathways. Here we use a combination of yeast two-hybrid screening, a high copy suppressor selection with a SUMO isopeptidase mutant, and tandem mass spectrometry to define a large set of proteins (>150) that can be modified by SUMO in budding yeast. These three approaches yielded overlapping sets of proteins with the most extensive set by far being those identified by mass spectrometry. The two-hybrid data also yielded a potential SUMO-binding motif. Functional categories of SUMO-modified proteins include SUMO conjugation system enzymes, chromatin-and gene silencingrelated factors, DNA repair and genome stability proteins, stress-related proteins, transcription factors, proteins involved in translation and RNA metabolism, and a variety of metabolic enzymes. The results point to a surprisingly broad array of cellular processes regulated by SUMO conjugation and provide a starting point for detailed studies of how SUMO ligation contributes to these different regulatory mechanisms.
Global SUMOylation on active chromatin is an acute heat stress response restricting transcription
Genome Biology, 2015
Background: Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription.
SUMO suppresses and MYC amplifies transcription globally by regulating CDK9 sumoylation
Cell research, 2018
Regulation of transcription is fundamental to the control of cellular gene expression and function. Although recent studies have revealed a role for the oncoprotein MYC in amplifying global transcription, little is known as to how the global transcription is suppressed. Here we report that SUMO and MYC mediate opposite effects upon global transcription by controlling the level of CDK9 sumoylation. On one hand, SUMO suppresses global transcription via sumoylation of CDK9, the catalytic subunit of P-TEFb kinase essential for productive transcriptional elongation. On the other hand, MYC amplifies global transcription by antagonizing CDK9 sumoylation. Sumoylation of CDK9 blocks its interaction with Cyclin T1 and thus the formation of active P-TEFb complex. Transcription profiling analyses reveal that SUMO represses global transcription, particularly of moderately to highly expressed genes and by generating a sumoylation-resistant CDK9 mutant, we confirm that sumoylation of CDK9 inhibits...
Proteotoxic stress reprograms the chromatin landscape of SUMO modification
Science Signaling, 2015
The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure of cells to heat shock or other forms of proteotoxic stress induces the conjugation of SUMO-2 to proteins in the nucleus. Here, we investigated the chromatin landscape of SUMO-2 modifications in response to heat stress. Through chromatin immunoprecipitation assays coupled to high-throughput DNA sequencing and with mRNA sequencing, we showed that in response to heat shock, SUMO-2 accumulated at nucleosome-depleted, active DNA-regulatory elements, which represented binding sites for large protein complexes and were predominantly associated with active genes. However, SUMO did not act as a direct transcriptional repressor or activator of these genes during heat shock. Instead, integration of our results with published proteomics data on heat shock-induced SUMO-2 substrates supports a model in which the conjugation of SUMO-2 to proteins acts as an acute stress response that is required for the stability of protein complexes involved in gene expression and posttranscriptional modification of mRNA. We showed that the conjugation of SUMO-2 to chromatin-associated proteins is an integral component of the proteotoxic stress response, and propose that SUMO-2 fulfills its essential role in cell survival by contributing to the maintenance of protein complex homeostasis.