The yeastUME6gene product is required for transcriptional repression mediated by theCAR1URS1repressor binding site

Park, Heui-Dong; Luche, Ralf M.; Cooper, Terrance G.

doi:10.1093/nar/20.8.1909

Cited by 90 publications

(122 citation statements)

References 32 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…To identify candidate transcriptional regulators of ATG8, we analyzed its promoter region and identified an upstream regulatory sequence, URS1, which is a consensus binding site for the transcription factor Ume6 (Fig. 1A), which was previously identified during a whole-genome microarray analysis (9)(10)(11). The URS1 consensus site consists of two invariant GGC repeats, which tend to be immediately preceded by a C and several T nucleotides and followed by a T and two A nucleotides, although some variability exists in these positions (9).…”

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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…GAT1-lacZ fusion plasmid pTSC624 was constructed by cloning a 0.87-kb PCR-generated GAT1 fragment (Ϫ670 to ϩ187; Gat1 residue 61) into SalI-BamHI-digested lacZ vector pHP41 (52). Plasmids pRA71, pRA72, pRA73, and pRA75 were constructed by cloning synthetic wild type and indicated substitution mutant DNA fragments covering GAT1 promoter sequences Ϫ250 to Ϫ200, containing the five clustered UAS GATA elements, into heterologous expression vector pHP41 (52) digested with Sal1 and Eag1.…”

Section: Strains Andmentioning

confidence: 99%

“…Plasmids pRA71, pRA72, pRA73, and pRA75 were constructed by cloning synthetic wild type and indicated substitution mutant DNA fragments covering GAT1 promoter sequences Ϫ250 to Ϫ200, containing the five clustered UAS GATA elements, into heterologous expression vector pHP41 (52) digested with Sal1 and Eag1. All plasmid structures were verified by DNA sequencing.…”

Section: Strains Andmentioning

confidence: 99%

Constitutive and Nitrogen Catabolite Repression-sensitive Production of Gat1 Isoforms

Rai

Tate

Georis

et al. 2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…The UME6 gene in Saccharomyces cerevisiae is a major regulator mediating some of these responses. UME6 encodes a DNA-binding protein (1,2) that associates with the upstream regulatory sequence URS1 A (consensus 5Ј-TCGGCGGCT-3Ј) to regulate transcription of genes responding to metabolites such as glucose, nitrogen and inositol (3)(4)(5)(6)(7)(8) and, in some cases, with a noncanonical URS1 (URS1 B ; 5Ј-SGWGGMRRNANW-3Ј) to regulate genes involved in DNA repair (9). Although Ume6 is dispensable for growth, it controls efficient mating of haploids and is essential for the initiation and progression of meiosis (2,10).…”

mentioning

confidence: 99%

The Ume6 regulon coordinates metabolic and meiotic gene expression in yeast

Williams

Primig

Washburn

et al. 2002

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

113

121

View full text Add to dashboard Cite

The Ume6 transcription factor in yeast is known to both repress and activate expression of diverse genes during growth and meiotic development. To obtain a more complete profile of the functions regulated by this protein, microarray analysis was used to examine transcription in wild-type and ume6⌬ diploids during vegetative growth in glucose and acetate. Two different genetic backgrounds (W303 and SK1) were examined to identify a core set of strain-independent Ume6-regulated genes. Among genes whose expression is controlled by Ume6 in both backgrounds, 82 contain homologies to the Ume6-binding site (URS1) and are expected to be directly regulated by Ume6. The vast majority of those whose functions are known participate in carbon͞nitrogen metabolism and͞or meiosis. Approximately half of the Ume6 direct targets are induced during meiosis, with most falling into the early meiotic expression class (cluster 4), and a smaller subset in the middle and later classes (clusters 5-7). Based on these data, we propose that Ume6 serves a unique role in diploid cells, coupling metabolic responses to nutritional cues with the initiation and progression of meiosis. Finally, expression patterns in the two genetic backgrounds suggest that SK1 is better adapted to respiration and W303 to fermentation, which may in part account for the more efficient and synchronous sporulation of SK1.

show abstract

The yeastUME6gene product is required for transcriptional repression mediated by theCAR1URS1repressor binding site

Cited by 90 publications

References 32 publications

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

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

Constitutive and Nitrogen Catabolite Repression-sensitive Production of Gat1 Isoforms

The Ume6 regulon coordinates metabolic and meiotic gene expression in yeast

Contact Info

Product

Resources

About