Chromatin Modulation at the FLO11 Promoter of <i>Saccharomyces cerevisiae</i> by HDAC and Swi/Snf Complexes

Barrales, Ramón R.; Korber, Philipp; Jiménez, Juan; Ibeas, José I.

doi:10.1534/genetics.112.140301

Cited by 23 publications

(23 citation statements)

References 51 publications

(77 reference statements)

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“…The probability that any given ORF would be regulated by all four of these transcription factors, by chance, is 1.21 × 10 −5 (Extended Experimental Procedures available online). Notably, FLO11 is also regulated by the chromatin-remodeling factor Swi1 (Barrales et al, 2012), yet another type of transcriptional regulator that is capable of forming a prion (Du et al, 2008). Other transcription factors are likely to be prions.…”

Section: Resultsmentioning

confidence: 99%

Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion

Holmes

Lancaster

Lindquist

et al. 2013

Cell

159

171

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SUMMARY Prion proteins undergo self-sustaining conforma-tional conversions that heritably alter their activities. Many of these proteins operate at pivotal positions in determining how genotype is translated into pheno-type. But the breadth of prion influences on biology and their evolutionary significance are just beginning to be explored. We report that a prion formed by the Mot3 transcription factor, [MOT3+], governs the acquisition of facultative multicellularity in the budding yeast Saccharomyces cerevisiae. The traits governed by [MOT3+] involved both gains and losses of Mot3 regulatory activity. [MOT3+]-dependent expression of FLO11, a major determinant of cell-cell adhesion, produced diverse lineage-specific multicellular phenotypes in response to nutrient deprivation. The prions themselves were induced by ethanol and eliminated by hypoxia—conditions that occur sequentially in the natural respiro-fermen-tative cycles of yeast populations. These data demonstrate that prions can act as environmentally responsive molecular determinants of multicellularity and contribute to the natural morphological diversity of budding yeast.

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Section: Resultsmentioning

confidence: 99%

Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion

Holmes

Lancaster

Lindquist

et al. 2013

Cell

159

171

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“…At least five prion proteins, Ure2, Swi1, Cyc8, Mot3, and Sfp1, the protein determinants of [URE3], [ SWI + ], [ OCT + ], [ MOT3 + ], and [ ISP + ] (Alberti et al, 2009; Du et al, 2008; Patel et al, 2009; Rogoza et al, 2010; Wickner, 1994), respectively, are potential transcriptional regulators of the FLO genes (Barrales et al, 2012). Recently, [ MOT3 + ], the prion form of Mot3, a transcriptional repressor, has been shown to promote yeast multicellular growth, possibly through de-repression of FLO11 (Holmes et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Yeast Prion [SWI+] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression

Zhang

2015

Cell Reports

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Summary While transcription factors are prevalent among yeast prion proteins, the role of prion-mediated transcriptional regulation remains elusive. We show here that the yeast prion [SWI+] abolishes flocculin (FLO) gene expression and results in a complete loss of multicellularity. Further investigation demonstrates that besides Swi1, multiple other proteins essential for FLO expression, including Mss11, Sap30, and Msn1 also undergo conformational changes, and become inactivated in [SWI+] cells. Moreover, the asparagine-rich region of Mss11 can exist as prion-like aggregates specifically in [SWI+] cells, which are SDS-resistant, heritable, and curable, but become metastable after separation from [SWI+]. Our findings thus reveal a prion-mediated mechanism through which multiple regulators in a biological pathway can be inactivated. In combination with the partial loss-of-function phenotypes of [SWI+] cells on non-glucose sugar utilization, our data therefore demonstrate that a prion can influence differently on distinct traits through multi-level regulations, providing insights into the biological roles of prions.

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“…These signaling pathways converge to either downregulate transcriptional repressors or stimulate transcriptional activators leading to FLO11 transcription. Additionally, FLO11 transcription is subject to multiple types of "epigenetic control" including a ncRNA toggle, histone deacetylation, and chromatin-remodeling proteins (Bumgarner et al 2009(Bumgarner et al , 2012Barrales et al 2012).…”

mentioning

confidence: 99%

Fine-Tuning of Histone H3 Lys4 Methylation During Pseudohyphal Differentiation by the CDK Submodule of RNA Polymerase II

Law

Ciccaglione

2014

Genetics

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Transcriptional regulation is dependent upon the interactions between the RNA pol II holoenzyme complex and chromatin. RNA pol II is part of a highly conserved multiprotein complex that includes the core mediator and CDK8 subcomplex. In Saccharomyces cerevisiae, the CDK8 subcomplex, composed of Ssn2p, Ssn3p, Ssn8p, and Srb8p, is thought to play important roles in mediating transcriptional control of stress-responsive genes. Also central to transcriptional control are histone post-translational modifications. Lysine methylation, dynamically balanced by lysine methyltransferases and demethylases, has been intensively studied, uncovering significant functions in transcriptional control. A key question remains in understanding how these enzymes are targeted during stress response. To determine the relationship between lysine methylation, the CDK8 complex, and transcriptional control, we performed phenotype analyses of yeast lacking known lysine methyltransferases or demethylases in isolation or in tandem with SSN8 deletions. We show that the RNA pol II CDK8 submodule components SSN8/SSN3 and the histone demethylase JHD2 are required to inhibit pseudohyphal growth-a differentiation pathway induced during nutrient limitation-under rich conditions. Yeast lacking both SSN8 and JHD2 constitutively express FLO11, a major regulator of pseudohyphal growth. Interestingly, deleting known FLO11 activators including FLO8, MSS11, MFG1, TEC1, SNF1, KSS1, and GCN4 results in a range of phenotypic suppression. Using chromatin immunoprecipitation, we found that SSN8 inhibits H3 Lys4 trimethylation independently of JHD2 at the FLO11 locus, suggesting that H3 Lys4 hypermethylation is locking FLO11 into a transcriptionally active state. These studies implicate the CDK8 subcomplex in finetuning H3 Lys4 methylation levels during pseudohyphal differentiation.?

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Chromatin Modulation at the FLO11 Promoter of Saccharomyces cerevisiae by HDAC and Swi/Snf Complexes

Cited by 23 publications

References 51 publications

Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion

Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion

The Yeast Prion [SWI+] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression

Fine-Tuning of Histone H3 Lys4 Methylation During Pseudohyphal Differentiation by the CDK Submodule of RNA Polymerase II

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