Comprehensive phenotypic analysis of single‐gene deletion and overexpression strains of <i>Saccharomyces cerevisiae</i>

Yoshikawa, Katsunori; Tanaka, Tadamasa; Ida, Yoshihiro; Furusawa, Chikara; Hirasawa, Takashi; Shimizu, Hiroshi

doi:10.1002/yea.1843

Cited by 126 publications

(120 citation statements)

References 37 publications

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“…Overexpression of TAF1, TAF3, TAF7, TAF8, and TAF14 resulted in dominant negative growth phenotypes, consistent with published results (75). As expected, overexpression of TAF2 could complement growth for all taf2 ts variants ( Fig.…”

Section: Journal Of Biological Chemistry 22723supporting

confidence: 91%

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

Feigerle

Weil

2016

Journal of Biological Chemistry

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The evolutionarily conserved RNA polymerase II transcription factor D (TFIID) complex is composed of TATA box-binding protein (TBP) and 13 TBP-associated factors (Tafs). The mechanisms by which many Taf subunits contribute to the essential function of TFIID are only poorly understood. To address this gap in knowledge, we present the results of a molecular genetic dissection of the TFIID subunit Taf2. Through systematic site-directed mutagenesis, we have discovered 12 taf2 temperature-sensitive (ts) alleles. Two of these alleles display growth defects that can be strongly suppressed by overexpression of the yeast-specific TFIID subunit TAF14 but not by overexpression of any other TFIID subunit. In Saccharomyces cerevisiae, Taf14 is also a constituent of six other transcription-related complexes, making interpretation of its role in each of these complexes difficult. Although Taf14 is not conserved as a TFIID subunit in metazoans, it is conserved through its chromatinbinding YEATS domain. Based on the Taf2-Taf14 genetic interaction, we demonstrate that Taf2 and Taf14 directly interact and mapped the Taf2-Taf14 interaction domains. We used this information to identify a Taf2 separation-of-function variant (Taf2-⌬C). Although Taf2-⌬C no longer interacts with Taf14 in vivo or in vitro, it stably incorporates into the TFIID complex. In addition, purified Taf2-⌬C mutant TFIID is devoid of Taf14, making this variant a powerful reagent for determining the role of Taf14 in TFIID function. Furthermore, we characterized the mechanism through which Taf14 suppresses taf2 ts alleles, shedding light on how Taf2-Taf14 interaction contributes to TFIID complex organization and identifying a potential role for Taf14 in mediating TFIID-chromatin interactions.RNA polymerase II and the general RNA polymerase II transcription factors (TFIIA,

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Section: Journal Of Biological Chemistry 22723supporting

confidence: 91%

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

Feigerle

Weil

2016

Journal of Biological Chemistry

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“…Most highly expressed genes in yeast are not subject to complete dosage compensation when mutated (34), but feedback at the gene level may be particularly common among transcription factors (35,36). In light of our evidence that feedback may serve to constrain the deleterious effects of misregulation among transcription factors, a model invoking especially strong pressures for such feedback control would be consistent with the extreme overexpression toxicity observed across transcription factors in yeast (31). The emerging picture is one in which both gene-and pathway-level feedback, at transcription factor genes and elsewhere in the yeast network, may be key elements of the architecture that mediates buffering of genetic change.…”

Section: Discussionsupporting

confidence: 57%

“…S3). To test the relationship between expression homeostasis and feedback more generally, we used growth rates of yeast strains manipulated to overexpress each transcription factor in turn (31). We first integrated these data with the results of our reporter-based screen for feedback among transcription factors (Fig.…”

Section: Resultsmentioning

confidence: 99%

Negative feedback confers mutational robustness in yeast transcription factor regulation

Denby

et al. 2012

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

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Organismal fitness depends on the ability of gene networks to function robustly in the face of environmental and genetic perturbations. Understanding the mechanisms of this stability is one of the key aims of modern systems biology. Dissecting the basis of robustness to mutation has proven a particular challenge, with most experimental models relying on artificial DNA sequence variants engineered in the laboratory. In this work, we hypothesized that negative regulatory feedback could stabilize gene expression against the disruptions that arise from natural genetic variation. We screened yeast transcription factors for feedback and used the results to establish ROX1 (Repressor of hypOXia) as a model system for the study of feedback in circuit behaviors and its impact across genetically heterogeneous populations. Mutagenesis experiments revealed the mechanism of Rox1 as a direct transcriptional repressor at its own gene, enabling a regulatory program of rapid induction during environmental change that reached a plateau of moderate steady-state expression. Additionally, in a given environmental condition, Rox1 levels varied widely across genetically distinct strains; the ROX1 feedback loop regulated this variation, in that the range of expression levels across genetic backgrounds showed greater spread in ROX1 feedback mutants than among strains with the ROX1 feedback loop intact. Our findings indicate that the ROX1 feedback circuit is tuned to respond to perturbations arising from natural genetic variation in addition to its role in induction behavior. We suggest that regulatory feedback may be an important element of the network architectures that confer mutational robustness across biology.R obustness of organismal function in the face of perturbations is critical for fitness. Since the seminal work of Waddington (1), biologists have remarked on the stability of phenotypes against environmental and genetic variation, and understanding how organisms achieve robustness remains one of the major challenges in systems biology (2-4). Much of the search for molecular mechanisms of robustness has focused on gene regulation. Characteristics of regulatory networks that confer robustness include pathway redundancy and master regulatory organization (5), phenotypic capacitors (6-8), paired activating and inhibiting inputs (9), and cooperative and feed-forward regulation (10). Additionally, negative regulatory feedback, in which a biomolecule represses its own abundance, can buffer variation in gene expression (11,12), and negative feedback loops have been shown to underlie robustness to variable environmental conditions and stochastic intracellular change (13-15). Negative feedback may also confer network stability against the effects of mutations (3, 16), but evidence for negative feedback as a driver of mutational robustness in vivo has been at a premium (17); the relevance of this principle to natural genetic variation remains largely unknown.In this work, we focused on negative feedback in yeast hypoxia regulation motiva...

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“…Consistent with this notion, switch genes are significantly enriched for dosagesensitive genes reported to result in cell cycle delay and/or growth defects when overexpressed. 65,66 Moreover, analysis of transcription induction upon replication stress showed that this group of genes is enriched for genes that are upregulated during replication stress conditions. 13,51 Switch Genes as DosageSensitive Checkpoint Effectors TOS genes.…”

Section: "Switch Genes:" a New Class Of G 1 /S Cell Cycle Genesmentioning

confidence: 99%

“…69 TOS4, MCD1, SWE1 and ACM1 are cell cycle-regulated, and, corroborating our hypothesis that switch genes expression needs to be tightly regulated, overexpression of these genes was linked to growth defect and/or cell cycle arrest. 65,66 Further analysis of the other switch genes, such as the TOS genes and eight putative ORFs, will show their potential role as checkpoint effectors.…”

Section: "Switch Genes:" a New Class Of G 1 /S Cell Cycle Genesmentioning

confidence: 99%

The checkpoint transcriptional response: Make sure to turn it off once you are satisfied

Smolka¹,

Oliveira²,

Harris³

et al. 2012

Cell Cycle

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and r.debruin@ucl.uc.uk T he replication checkpoint signaling network monitors the presence of replication-induced lesions to DNA and coordinates an elaborate cellular response that includes ample transcriptional reprogramming. Recent work has established two major groups of replication stressinduced genes in Saccharomyces cerevisiae, the DNA damage response (DDR) genes and G 1 /S cell cycle (CC) genes. In both cases, transcriptional activation is mediated via checkpoint-dependent inhibition of a transcriptional repressor (Crt1 for DDR and Nrm1 for CC) that participates in negative feedback regulation. This repressor-mediated regulation enables transcription to be rapidly repressed once cells have dealt with the replication stress. The recent finding of a new class of CC genes, named "switch genes," further uncovers a mode of transcription regulation that prevents overexpression of replication stress induced genes during G 1 . Collectively, these findings highlight the need for mechanisms that tightly control replication stress-induced transcription, allowing rapid transcriptional activation during replication stress but also avoiding longterm hyperaccumulation of the induced protein product that may be detrimental to cell proliferation.

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Comprehensive phenotypic analysis of single‐gene deletion and overexpression strains of Saccharomyces cerevisiae

Cited by 126 publications

References 37 publications

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex

Negative feedback confers mutational robustness in yeast transcription factor regulation

The checkpoint transcriptional response: Make sure to turn it off once you are satisfied

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