The yeast Cyc8–Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene

Fleming, Alastair B.; Beggs, Suzanne; Church, Michael; Tsukihashi, Yoshihiro; Pennings, Sari

doi:10.1016/j.bbagrm.2014.07.022

Cited by 45 publications

(92 citation statements)

References 71 publications

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“…RNA-seq data of all the HXT genes were confirmed by quantitative PCR (qPCR) (data not shown). Of the 93 upregulated genes, 34 are located in the 30 kbp of the telomeric regions of the various chromosomes, which is consistent with data published before (25).…”

Section: Resultssupporting

confidence: 81%

Improved Xylose Metabolism by a CYC8 Mutant of Saccharomyces cerevisiae

Nijland

Shin

Boender

et al. 2017

Appl Environ Microbiol

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Engineering Saccharomyces cerevisiae for the utilization of pentose sugars is an important goal for the production of second-generation bioethanol and biochemicals. However, S. cerevisiae lacks specific pentose transporters, and in the presence of glucose, pentoses enter the cell inefficiently via endogenous hexose transporters (HXTs). By means of in vivo engineering, we have developed a quadruple hexokinase deletion mutant of S. cerevisiae that evolved into a strain that efficiently utilizes D-xylose in the presence of high D-glucose concentrations. A genome sequence analysis revealed a mutation (Y353C) in the general corepressor CYC8, or SSN6, which was found to be responsible for the phenotype when introduced individually in the nonevolved strain. A transcriptome analysis revealed altered expression of 95 genes in total, including genes involved in (i) hexose transport, (ii) maltose metabolism, (iii) cell wall function (mannoprotein family), and (iv) unknown functions (seripauperin multigene family). Of the 18 known HXTs, genes for 9 were upregulated, especially the low or nonexpressed HXT10, HXT13, HXT15, and HXT16. Mutant cells showed increased uptake rates of D-xylose in the presence of D-glucose, as well as elevated maximum rates of metabolism (V max ) for both D-glucose and D-xylose transport. The data suggest that the increased expression of multiple hexose transporters renders D-xylose metabolism less sensitive to D-glucose inhibition due to an elevated transport rate of D-xylose into the cell. IMPORTANCEThe yeast Saccharomyces cerevisiae is used for second-generation bioethanol formation. However, growth on xylose is limited by pentose transport through the endogenous hexose transporters (HXTs), as uptake is outcompeted by the preferred substrate, glucose. Mutant strains were obtained with improved growth characteristics on xylose in the presence of glucose, and the mutations mapped to the regulator Cyc8. The inactivation of Cyc8 caused increased expression of HXTs, thereby providing more capacity for the transport of xylose, presenting a further step toward a more robust process of industrial fermentation of lignocellulosic biomass using yeast.KEYWORDS sugar transporter, xylose transport, evolutionary engineering, transcriptome, yeast A n increasing energy demand and concerns of obtaining this energy from fossil fuels have stimulated the development of liquid fuels from renewable feedstock. Bioethanol, mostly used as a fuel additive, produced from readily fermentable agricultural feedstocks, such as sugar cane and corn, is less desired because the production of these feedstocks requires large amounts of arable land and competes with the food supply (1). A more sustainable source of feedstock is lignocellulosic biomass from hardwood, softwood, and agricultural residues (2). However, a major drawback of lignocellulosic feedstocks is the inability of the most commonly used yeast in industry,

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Section: Resultssupporting

confidence: 81%

Improved Xylose Metabolism by a CYC8 Mutant of Saccharomyces cerevisiae

Nijland

Shin

Boender

et al. 2017

Appl Environ Microbiol

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“…In the absence of Tup1–Cyc8, FLO1 de-repression is accompanied by histone acetylation and a gross disruption of the promoter chromatin which includes extensive nucleosome repositioning and loss (13,26,30). The Swi–Snf complex was implicated in this nucleosome rearrangement and FLO1 gene de-repression, since in a cyc8 snf2 double mutant, both remodeling and FLO1 transcription are absent (26).…”

Section: Introductionmentioning

confidence: 99%

Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressedFLO1gene

Church¹,

Smith²,

Alhussain³

et al. 2017

Nucleic Acids Res

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The Saccharomyces cerevisiae FLO1 gene encodes a cell wall protein that imparts cell–cell adhesion. FLO1 transcription is regulated via the antagonistic activities of the Tup1–Cyc8 co-repressor and Swi–Snf co-activator complexes. Tup1–Cyc8 represses transcription through the organization of strongly positioned, hypoacetylated nucleosomes across gene promoters. Swi–Snf catalyzes remodeling of these nucleosomes in a mechanism involving histone acetylation that is poorly understood. Here, we show that FLO1 de-repression is accompanied by Swi–Snf recruitment, promoter histone eviction and Sas3 and Ada2(Gcn5)-dependent histone H3K14 acetylation. In the absence of H3K14 acetylation, Swi–Snf recruitment and histone eviction proceed, but transcription is reduced, suggesting these processes, while essential, are not sufficient for de-repression. Further analysis in the absence of H3K14 acetylation reveals RNAP II recruitment at the FLO1 promoter still occurs, but RNAP II is absent from the gene-coding region, demonstrating Sas3 and Ada2-dependent histone H3 acetylation is required for transcription elongation. Analysis of the transcription kinetics at other genes reveals shared mechanisms coupled to a distinct role for histone H3 acetylation, essential at FLO1, downstream of initiation. We propose histone H3 acetylation in the coding region provides rate-limiting control during the transition from initiation to elongation which dictates whether the gene is permissive for transcription.

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“…However, the mechanism by which Tup1 associates with IME1 is unclear, and whether it recruits other chromatin factors has not yet been investigated. Tup1 has been shown to play diverse roles at other nutrient-responsive promoters, such as driving the association of HDACs with FLO1 [51, 52] and cooperating with the SWR1 complex for deposition of H2A.Z (Htz1) at the GAL1 and SUC2 promoters [53]. As a repressor of IME1 , Tup1 has been linked to nutrient-sensing through PKA and TOR complex signaling networks [50], whereas Rme1 levels are responsive to mating type and ploidy [42, 54, 55].…”

Section: Nutrient-responsive Signaling and Chromatin Statesmentioning

confidence: 99%

Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate

Jaiswal

Turniansky

Green

2017

Journal of Molecular Biology

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When yeast cells are challenged by a fluctuating environment, signaling networks activate differentiation programs that promote their individual or collective survival. These programs include the initiation of meiotic sporulation, the formation of filamentous growth structures and the activation of programmed cell death pathways. The establishment and maintenance of these distinct cell fates are driven by massive gene expression programs that promote the necessary changes in morphology and physiology. While these genomic reprogramming events depend on a specialized network of transcription factors, a diverse set of chromatin regulators, including histone-modifying enzymes, chromatin remodelers and histone variants, also play essential roles. Here, we review the broad functions of histone modifications in initiating cell fate transitions, with particular focus on their contribution to the control of expression of key genes required for the differentiation programs and chromatin reorganization that accompanies these cell fates.

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The yeast Cyc8–Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene

Cited by 45 publications

References 71 publications

Improved Xylose Metabolism by a CYC8 Mutant of Saccharomyces cerevisiae

Improved Xylose Metabolism by a CYC8 Mutant of Saccharomyces cerevisiae

Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressedFLO1gene

Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate

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