Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment

Bumgarner, Stacie L.; Neuert, Gregor; Voight, Benjamin F.; Symbor-Nagrabska, Anna; Grisafi, Paula; Oudenaarden, Alexander van; Fink, Gerald R.

doi:10.1016/j.molcel.2011.11.029

Cited by 103 publications

(94 citation statements)

References 39 publications

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“…Rpd3 activates FLO11 expression by repression of ICR1 ncRNA and Sfl1 has the opposite role (Bumgarner et al 2009(Bumgarner et al , 2012. We have observed that this effect of Rpd3 is not shared by Hos2, suggesting that this effect may be the additional mechanism independent of Hos2 observed for Rpd3.…”

Section: Activation Of Flo11 By Both Rpd3 and Hos2mentioning

confidence: 65%

“…Sfl1 activates ICR1 ncRNA transcription by repressing the transcription of PWR1 ncRNA that partially interferes with the ICR1 one. In this interesting regulatory mechanism, the Rpd3L complex has been described to have the opposite role (Bumgarner et al 2009(Bumgarner et al , 2012. We carried out qRT-PCR to study the level of ICR1 ncRNA in mutants from both backgrounds ( Figure 6B) and to study the effect of histone deacetylases and Sfl1 over this regulation.…”

Section: Deacetylase Activity Of Rpd3 Is Required For Flo11 Expressionmentioning

confidence: 99%

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

et al. 2012

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Cell adhesion and biofilm formation are critical processes in the pathogenicity of fungi and are mediated through a family of adhesin proteins conserved throughout yeasts and fungi. In Saccharomyces cerevisiae, Flo11 is the main adhesin involved in cell adhesion and biofilm formation, making the study of its function and regulation in this nonpathogenic budding yeast highly relevant. The S. cerevisiae FLO11 gene is driven by a TATA-box-containing promoter that is regulated through one of the longest regulatory upstream regions (3 kb) in yeast. We reported recently that two chromatin cofactor complexes, the Rpd3L deacetylase and the Swi/Snf chromatin-remodeling complexes, contribute significantly to the regulation of FLO11. Here, we analyze directly how these complexes impact on FLO11 promoter chromatin structure and dissect further the interplay between histone deacetylases, chromatin remodeling, and the transcriptional repressor Sfl1. We show that the regulation of chromatin structure represents an important layer of control in the highly complex regulation of the FLO11 promoter.

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Section: Activation Of Flo11 By Both Rpd3 and Hos2mentioning

confidence: 65%

Section: Deacetylase Activity Of Rpd3 Is Required For Flo11 Expressionmentioning

confidence: 99%

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

et al. 2012

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“…This repression of IME1 by IRT1 transcription is dependent on Set2 methyltransferase and Set3 deacetylase, suggesting that histone modifications are critical here. The FLO11 gene encodes a cell wall protein regulating adhesion between cells, and its expression is controlled by a pair of lncRNAs from the upstream region (24). lncRNAs have been proposed to regulate gene induction at the PHO5 (22) and GAL loci (21,52).…”

Section: Discussionmentioning

confidence: 99%

“…Long noncoding RNAs (lncRNAs) can regulate transcription (14)(15)(16)(17), and in budding yeast lncRNAs have been implicated in promoter regulation (18)(19)(20)(21)(22)(23)(24). Here we decipher the mechanism by which mating pheromone blocks expression of the HO endonuclease during the subsequent cell cycle.…”

Section: Significancementioning

confidence: 99%

Disruption of promoter memory by synthesis of a long noncoding RNA

Yarrington

Chuong

et al. 2016

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

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The yeast HO endonuclease is expressed in late G1 in haploid mother cells to initiate mating-type interconversion. Cells can be arrested in G1 by nutrient deprivation or by pheromone exposure, but cells that resume cycling after nutrient deprivation or cyclindependent kinase (CDK) inactivation express HO in the first cell cycle, whereas HO is not expressed until the second cycle after release from pheromone arrest. Here, we show that transcription of a long noncoding RNA (lncRNA) mediates this differential response. The SBF and Mediator factors remain bound to the inactive promoter during arrest due to CDK inactivation, and these bound factors allow the cell to remember a transcriptional decision made before arrest. If the presence of mating pheromone indicates that this decision is no longer appropriate, a lncRNA originating at -2700 upstream of the HO gene is induced, and the transcription machinery displaces promoter-bound SBF, preventing HO transcription in the subsequent cell cycle. Further, we find that the displaced SBF is blocked from rebinding due to incorporation of its recognition sites within nucleosomes. Expressing the pHO-lncRNA in trans is ineffective, indicating that transcription in cis is required. Factor displacement during lncRNA transcription could be a general mechanism for regulating memory of previous events at promoters.lncRNA | nucleosomes | promoter memory | gene regulation | chromatin

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“…In addition to these pathways, FLO11 is also regulated by the pH response pathway, noncoding RNAs, and the chromatin state (Halme et al 2004;Barrales et al 2008Barrales et al , 2012Bumgarner et al 2009;Octavio et al 2009). A recent study showed that the noncoding RNAs contribute to a variegated transcription of FLO11 through the modulation of transcription factor recruitment (Bumgarner et al 2012).The FLO genes share a common structure, including a C-terminal glycosylphosphatidylinositol (GPI)-anchor addition site, an N-terminal carbohydrate-or peptide-binding domain or domain of unknown function, and a central domain containing multiple serine and threonine-rich repeats (Verstrepen and Klis 2006). The latter domain is also referred to as a domain with intragenic tandem repeats.…”

mentioning

confidence: 99%

Adaptation of the Osmotolerant Yeast Zygosaccharomyces rouxii to an Osmotic Environment Through Copy Number Amplification of FLO11D

2013

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Copy number variations (CNVs) contribute to the adaptation process in two possible ways. First, they may have a direct role, in which a certain number of copies often provide a selective advantage. Second, CNVs can also indirectly contribute to adaptation because a higher copy number increases the so-called "mutational target size." In this study, we show that the copy number amplification of FLO11D in the osmotolerant yeast Zygosaccharomyces rouxii promotes its further adaptation to a florformative environment, such as osmostress static culture conditions. We demonstrate that a gene, which was identified as FLO11D, is responsible for flor formation and that its expression is induced by osmostress under glucose-free conditions, which confer unique characteristics to Z. rouxii, such as osmostress-dependent flor formation. This organism possesses zero to three copies of FLO11D, and it appears likely that the FLO11D copy number increased in a branch of the Z. rouxii tree. The cellular hydrophobicity correlates with the FLO11D copy number, and the strain with a higher copy number of FLO11D exhibits a fitness advantage compared to a reference strain under osmostress static culture conditions. Our data indicate that the FLO gene-related system in Z. rouxii has evolved remarkably to adapt to osmostress environments.A N organism adapts to adverse environments to survive and produce progeny. Adaptive evolution is the process through which a population becomes better suited to its environment via mutation, selection, and random drift (Bürger 2000;Cressman 2003;Ewens 2004;Nowak and Sigmund 2004). Types of mutations include nucleotide changes (Steiner et al. 2007;Barrick and Lenski 2009), transposition events (Wilke and Adams 1992;Aminetzach et al. 2005), and copy number variations (CNVs), including gene amplifications (duplication) and deletions (Brown et al. 1998;Perry et al. 2007;Gresham et al. 2010). CNVs can have a phenotypic impact and can consequently alter the fitness of an allele through the following mechanisms: (i) changing the coding sequence of a gene (Yamanaka et al. 2009;Schlattl et al. 2011), (ii) creating paralogs that can diverge from each other and take on new or specialized functions (neofunctionalization or subfunctionalization, respectively) (Ohno 1970;Innan and Kondrashov 2010), and (iii) altering the expression level of a gene (gene dosage effect) (Stranger et al. 2007;Yamanaka et al. 2009;Iskow et al. 2012). In humans, most CNVs overlapping genes are under purifying (negative) selection (Conrad et al. 2010), but a handful of CNVs are thought to be under positive selection (Cooper et al. 2007;Hurles et al. 2010;Iskow et al. 2012) such as AMY1 (Perry et al. 2007). In yeast, there are several examples of how the (increased) copy number can provide a direct selective advantage (Gresham et al. 2008;Voordeckers et al. 2012).In nature, budding yeast exhibits a number of adaptive responses, such as filamentation, invasive growth, flocculation, and biofilm formation, to overcome a deleterious enviro...

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Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment

Cited by 103 publications

References 39 publications

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

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

Disruption of promoter memory by synthesis of a long noncoding RNA

Adaptation of the Osmotolerant Yeast Zygosaccharomyces rouxii to an Osmotic Environment Through Copy Number Amplification of FLO11D

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