Identification of the Sin3-Binding Site in Ume6 Defines a Two-Step Process for Conversion of Ume6 from a Transcriptional Repressor to an Activator in Yeast

Washburn, Brian K.; Esposito, Rochelle Easton

doi:10.1128/mcb.21.6.2057-2069.2001

Cited by 93 publications

(91 citation statements)

References 103 publications

(156 reference statements)

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“…In an ume6 deletion mutant, early meiosis-specific genes are derepressed during vegetative growth (24,29). Therefore we further confirmed the relationships between MSH4 transcription and ARS605 origin activity by introducing a deletion mutation of ume6 to the cell.…”

Section: Origin Activities Of Arss On Chromosome VI In Premeiotic S-psupporting

confidence: 63%

“…Transcription of MSH4 Interferes with Origin Activity of ARS605 in Mitosis-Induction of the early meiosis-specific gene family including MSH4 is dependent on the transcription factors Ime1 and Ume6 (29). In an ume6 deletion mutant, early meiosis-specific genes are derepressed during vegetative growth (24,29).…”

Section: Origin Activities Of Arss On Chromosome VI In Premeiotic S-pmentioning

confidence: 99%

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Perturbation of the Activity of Replication Origin by Meiosis-specific Transcription

Mori

Shirahige

2007

Journal of Biological Chemistry

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We have determined the activity of all ARSs on the Saccharomyces cerevisiae chromosome VI as chromosomal replication origins in premeiotic S-phase by neutral/neutral two-dimensional gel electrophoresis. The comparison of origin activity of each origin in mitotic and premeiotic S-phase showed that one of the most efficient origins in mitotic S-phase, ARS605, was completely inhibited in premeiotic S-phase. ARS605 is located within the open reading frame of MSH4 gene that is transcribed specifically during an early stage of meiosis. Systematic analysis of relationships between MSH4 transcription and ARS605 origin activity revealed that transcription of MSH4 inhibited the ARS605 origin activity by removing origin recognition complex from ARS605. Deletion of UME6, a transcription factor responsible for repressing MSH4 during mitotic S-phase, resulted in inactivation of ARS605 in mitosis. Our finding is the first demonstration that the transcriptional regulation on the replication origin activity is related to changes in cell physiology. These results may provide insights into changes in replication origin activity in embryonic cell cycle during early developmental stages.Eukaryotic chromosomes consist of multiple replication units. Each origin of DNA replication is strictly controlled to fire only once in the cell cycle in the fixed sequential order (1, 2). This temporal program for origin firing is utilized for the maintenance of genome integrity through DNA replication checkpoint mechanism (3, 4). It was shown that a checkpoint effector kinase Rad53 repressed firing of late origins when replication was perturbed by hydroxy urea or methyl methane sulfonate. Furthermore, recent genome-wide studies of eukaryotic chromosomal DNA replication using Saccharomyces cerevisiae have provided us with a kinetic map of progression of DNA replication along the chromosome (5, 6). However, these studies were restricted to DNA replication during mitotic cell cycle and little is known about how these multiple replication origins behave under different cell cycle, i.e. meiotic cell cycle.The decision to enter the meiotic cell cycle is made in G 1 phase and this affects the way in which the G 1 /S transition is controlled. In budding yeast (S. cerevisiae), poor nutrient conditions are the cue to embark on the meiotic cell cycle, which culminates in the production of spores (7). The replication of chromosome is the first detectable cytological event in meiosis. The coordinated synthesis of genomic DNA requires multiple levels of regulation and a large number of gene products. Genetic analysis in S. cerevisiae indicates that the replicative machinery used to synthesize DNA in vegetative cells is also required for the duplication of chromosome in meiosis (8 -10).In S. cerevisiae, mitotic S-phase and premeiotic S-phase appear to be differently regulated. For example, premeiotic S-phase is 1.5-2 times longer than mitotic S-phase (11). However, replication kinetics as measured by neutral/neutral twodimensional gel electrophoresis of 100-kb s...

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Section: Origin Activities Of Arss On Chromosome VI In Premeiotic S-psupporting

confidence: 63%

Section: Origin Activities Of Arss On Chromosome VI In Premeiotic S-pmentioning

confidence: 99%

Perturbation of the Activity of Replication Origin by Meiosis-specific Transcription

Mori

Shirahige

2007

Journal of Biological Chemistry

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“…We examined the promoter regions of other ATG genes and note that the gene encoding Atg23 also contains a potential URS1 site. Ume6 is a zinc cluster protein that both represses and activates transcription of a diverse set of genes involved in meiosis and metabolism in response to nutritional cues such as glucose, nitrogen, and inositol (9,(12)(13)(14). If Ume6 regulates Atg8, then a ume6Δ strain should have altered Atg8 protein levels.…”

Section: Resultsmentioning

confidence: 99%

Ume6 transcription factor is part of a signaling cascade that regulates autophagy

Bartholomew

Suzuki

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

101

123

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Autophagy has been implicated in a number of physiological processes important for human heath and disease. Autophagy involves the formation of a double-membrane cytosolic vesicle, an autophagosome. Central to the formation of the autophagosome is the ubiquitin-like protein autophagy-related (Atg)8 (microtubuleassociated protein 1 light chain 3/LC3 in mammalian cells). Following autophagy induction, Atg8 shows the greatest change in expression of any of the proteins required for autophagy. The magnitude of autophagy is, in part, controlled by the amount of Atg8; thus, controlling Atg8 protein levels is one potential mechanism for modulating autophagy activity. We have identified a negative regulator of ATG8 transcription, Ume6, which acts along with a histone deacetylase complex including Sin3 and Rpd3 to regulate Atg8 levels; deletion of any of these components leads to an increase in Atg8 and a concomitant increase in autophagic activity. A similar regulatory mechanism is present in mammalian cells, indicating that this process is highly conserved.lysosome | membrane biogenesis | phagophore | stress | vacuole M acroautophagy, hereafter referred to as autophagy, is an evolutionarily conserved process used by eukaryotic cells for the bulk degradation of intracellular proteins and organelles (1). Autophagy is not only vital for cell survival in nutrient-poor conditions (2) but is also linked to various physiological processes, including immune defense, tumor suppression, and prevention of neurodegeneration (3). Whereas autophagy plays a primarily protective role, it can also contribute to cell death; thus, the magnitude of autophagy must be carefully regulated.Central to autophagy is the formation of autophagosomes (4), double-membrane-bound structures that engulf and deliver cytoplasmic materials to the vacuole/lysosome for degradation. During autophagosome formation, the autophagy-related ubiquitin-like protein Atg8/microtubule-associated protein 1 light chain 3 (LC3) covalently modifies phosphatidylethanolamine (PE). Almost one-fourth of the characterized autophagy-related (Atg) proteins in yeast are involved in the formation or stability of Atg8-PE, which plays a critical role in controlling expansion of the phagophore (the initial sequestering membrane), and in determining autophagosome size, thereby regulating autophagy activity (5, 6). Upon starvation, the level of ATG8 mRNA sharply increases, leading to a subsequent induction of the Atg8 protein level (7,8). The increase in the amount of Atg8 during autophagy is critical for supplying a sufficient amount of this protein to maintain normal levels of autophagy; yeast strains deficient in Atg8 induction generate abnormally small autophagosomes (5). Thus, characterization of how Atg8 protein levels are modulated is of tremendous importance both in understanding the regulation of autophagy and for the elucidation of potential therapeutic targets. However, little is known about the mechanisms regulating ATG8 transcription. ResultsUme6-Sin3-Rpd3 Complex Represse...

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“…Ume6 in a complex with Sin3 and Rpd3 functions as a repressor; however, its interaction with Ime1 during meiosis converts Ume6 to an activator of early genes (29). The co-repressor Sin3 interacts with the deacetylase Rpd3 and causes repression by deacetylation of histones (30 -32).…”

Section: Discussionmentioning

confidence: 99%

Glucose-mediated Phosphorylation Converts the Transcription Factor Rgt1 from a Repressor to an Activator

Mosley¹,

Lakshmanan²,

Aryal

et al. 2003

Journal of Biological Chemistry

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Glucose, the most abundant carbon and energy source, regulates the expression of genes required for its own efficient metabolism. In the yeast Saccharomyces cerevisiae, glucose induces the expression of the hexose transporter (HXT) genes by modulating the activity of the transcription factor Rgt1 that functions as a repressor when glucose is absent. However, in the presence of high concentrations of glucose, Rgt1 is converted from a repressor to an activator and is required for maximal induction of HXT1 gene expression. We report that Rgt1 binds to the HXT1 promoter only in the absence of glucose, suggesting that Rgt1 increases HXT1 gene expression at high levels of glucose by an indirect mechanism. It is likely that Rgt1 stimulates the expression of an activator of the HXT1 gene at high concentrations of glucose. In addition, we demonstrate that Rgt1 becomes hyperphosphorylated in response to high glucose levels and that this phosphorylation event is required for Rgt1 to activate transcription. Furthermore, Rgt1 lacks the glucose-mediated phosphorylation in the snf3 rgt2 and grr1 mutants, which are defective in glucose induction of HXT gene expression. In these mutants, Rgt1 behaves as a constitutive repressor independent of the carbon source. We conclude that phosphorylation of Rgt1 in response to glucose is required to abolish the Rgt1-mediated repression of the HXT genes and to convert Rgt1 from a transcriptional repressor to an activator.The yeast Saccharomyes cerevisiae uses glucose as its preferred carbon and energy source. Glucose not only represses the expression of genes that are required for the metabolism of alternate sugars but also induces the transcription of genes that are essential for its own efficient utilization (1-3). Among the genes that are induced by glucose are the members of the HXT gene family, which encode glucose transporters. Glucose induces the expression of the HXT1-HXT4 genes by 10 -300-fold (4, 5).Several components of the glucose induction pathway required for HXT gene expression have been identified, including the glucose sensors Snf3 and Rgt2, that are responsible for sensing extracellular glucose and generating the intracellular signal (6, 7). A strain mutated for both sensors (snf3 rgt2 double mutant) is completely defective in glucose induction of the HXT gene expression (7). Another component that is absolutely essential for glucose induction of the HXT gene expression is the ubiquitin ligase Grr1 (5, 8). Two homologous proteins, Std1 and Mth1, have been shown to negatively regulate HXT gene expression and to interact with the carboxyl-terminal tails of the Snf3 and Rgt2 sensors (9 -11). Repression of HXT gene expression in the absence of glucose is abolished in a std1 mth1 double mutant (9, 11).The target of the glucose induction signal is the Cys 6 DNAbinding protein Rgt1, which belongs to the family of the Gal4 transcription factors (12). In the absence of glucose, Rgt1 represses HXT gene expression, whereas at high concentrations of glucose Rgt1 is required for maxima...

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Identification of the Sin3-Binding Site in Ume6 Defines a Two-Step Process for Conversion of Ume6 from a Transcriptional Repressor to an Activator in Yeast

Cited by 93 publications

References 103 publications

Perturbation of the Activity of Replication Origin by Meiosis-specific Transcription

Perturbation of the Activity of Replication Origin by Meiosis-specific Transcription

Ume6 transcription factor is part of a signaling cascade that regulates autophagy

Glucose-mediated Phosphorylation Converts the Transcription Factor Rgt1 from a Repressor to an Activator

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