Crystal structure of the WOPR-DNA complex and implications for Wor1 function in white-opaque switching of Candida albicans

Zhang, Shicheng; Zhang, Tianlong; Yan, Minmin; Ding, Jianping; Chen, Jiangye

doi:10.1038/cr.2014.102

Cited by 16 publications

(18 citation statements)

References 37 publications

(57 reference statements)

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“…The DNA binding site and protein crystal structure of several homologs of Sge1 have been resolved [33,41–43]. The amino acids interacting with DNA are highly conserved among Wor1/Sge1 homologs from different fungi [23,27,29,30,41,43,44]. Consistent with this, the DNA binding sites of Sge1 orthologs in Saccharomyces cerevisiae (Mit1) and the filamentous fungus Histoplasma capsulatum (Ryp1) are the same as for Wor1 [33].…”

Section: Resultsmentioning

confidence: 99%

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

et al. 2016

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Proteins secreted by pathogens during host colonization largely determine the outcome of pathogen-host interactions and are commonly called ‘effectors’. In fungal plant pathogens, coordinated transcriptional up-regulation of effector genes is a key feature of pathogenesis and effectors are often encoded in genomic regions with distinct repeat content, histone code and rate of evolution. In the tomato pathogen Fusarium oxysporum f. sp. lycopersici (Fol), effector genes reside on one of four accessory chromosomes, known as the ‘pathogenicity’ chromosome, which can be exchanged between strains through horizontal transfer. The three other accessory chromosomes in the Fol reference strain may also be important for virulence towards tomato. Expression of effector genes in Fol is highly up-regulated upon infection and requires Sge1, a transcription factor encoded on the core genome. Interestingly, the pathogenicity chromosome itself contains 13 predicted transcription factor genes and for all except one, there is a homolog on the core genome. We determined DNA binding specificity for nine transcription factors using oligonucleotide arrays. The binding sites for homologous transcription factors were highly similar, suggesting that extensive neofunctionalization of DNA binding specificity has not occurred. Several DNA binding sites are enriched on accessory chromosomes, and expression of FTF1, its core homolog FTF2 and SGE1 from a constitutive promoter can induce expression of effector genes. The DNA binding sites of only these three transcription factors are enriched among genes up-regulated during infection. We further show that Ftf1, Ftf2 and Sge1 can activate transcription from their binding sites in yeast. RNAseq analysis revealed that in strains with constitutive expression of FTF1, FTF2 or SGE1, expression of a similar set of plant-responsive genes on the pathogenicity chromosome is induced, including most effector genes. We conclude that the Fol pathogenicity chromosome may be partially transcriptionally autonomous, but there are also extensive transcriptional connections between core and accessory chromosomes.

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Section: Resultsmentioning

confidence: 99%

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

et al. 2016

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“…Here, we show that Wor1 is SUMOylated at K385 and this event is important for Wor1 function. Wor1 is a protein 785 amino acids in length, with a conserved N-terminal WOPR DNA binding domain (residues 5-321) and a long nonconserved C-terminus (Lohse et al, 2010;Zhang et al, 2014). SUMOylation at K385, which is located outside of the WOPR DNA binding domain, suggests that Wor1 SUMOylation may contribute to its association with other regulatory proteins.…”

Section: Wor1 Sumoylation Contributes To Wor1 Regulation In White To mentioning

confidence: 99%

“…Wor1 contains a conserved DNAbinding region at the N-terminus consisting of two conserved segments (WOPRa and WOPRb) connected by a non-conserved linker that can bind to specific DNA sequences of the promoter regions (Lohse et al, 2010). The sequentially separated WOPRa and WOPRb are structurally interwound together to form a compact globular domain termed WOPR domain (Zhang et al, 2014). The crystal structure of C. albicans Wor1 WOPR domain is highly conserved with that of Saccharomyces cerevisiae YHR177w WOPR domain (Lohse et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…The crystal structure of C. albicans Wor1 WOPR domain is highly conserved with that of Saccharomyces cerevisiae YHR177w WOPR domain (Lohse et al, 2014). The WOPR domain-DNA interactions are essential for WOR1 transcriptional regulation and white to opaque switching (Lohse et al, 2014;Zhang et al, 2014). Homologs of Wor1 have been found in many fungi to regulate key developmental processes.…”

Section: Introductionmentioning

confidence: 99%

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SUMOylation of Wor1 by a novel SUMO E3 ligase controls cell fate in Candida albicans

Yan

Nie

Wang

et al. 2015

Molecular Microbiology

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SummaryCandida albicans is the most common human fungal pathogen, yet is a normal commensal resident of the human gut. CO2 levels in the gut are much higher than in air, and it is known that elevated CO2 concentration promotes C. albicans cells to undergo a phenotypic switch from white to opaque phase. Wor1, the master regulator of opaque cell formation, is required for both the white to opaque transition and opaque maintenance. To elucidate the regulatory mechanism of Wor1, we set out to identify Wor1-interacting proteins using a yeast two-hybrid screen. A SUMO E3 ligase named Wos1 (Wor1 SUMO-ligase 1) was identified to interact with Wor1 and regulate Wor1 SUMOylation. WOS1 expression is upregulated in response to high CO2, and the induction by CO2 is dependent on the transcription factor Flo8. Under high CO2 conditions, Wos1 is required for the white to opaque switch and acts downstream of Flo8. At atmospheric CO2 levels, overexpression of Wos1 enhances Wor1 SUMOylation and promotes the white to opaque switch. Wor1 is found to be SUMOylated at lysine 385, and loss of this mark by point mutation leads to a defect in CO2-mediated opaque cell induction. Together, our genetic and biological data show that Wos1-mediated Wor1 SUMOylation contributes to the regulation of CO2-induced white to opaque switching as well as heritable maintenance of the opaque cell type.

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“…The deletion itself is outof-frame, and therefore results in a modified C-terminus of the protein, including a premature stop codon and truncation of the final product. From the extensive literature on the MIT1 ortholog in C. albicans, WOR1, we know that DNA binding activity is likely confined to the N-terminal portion of the protein, far from the mutation in this allele of MIT1: in WOR1, two DNA binding regions in the N-terminal portion of the protein are sufficient for full activity (Lohse et al 2010;Zhang et al 2014). WOR1 and MIT1 also both have a self-regulatory mechanism through a positive feedback loop-a potential mechanism for the enhanced function implicated by the mutation we observe (Zordan et al 2006;Cain et al 2012).…”

Section: Functional Flo1 Is Necessary For Flocculation Driven By Rox3mentioning

confidence: 99%

Experimental evolution reveals favored adaptive routes to cell aggregation in yeast

Hope

Amorosi

Miller

et al. 2016

Preprint

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Yeast flocculation is a community-building cell aggregation trait that is an important mechanism of stress resistance and a useful phenotype for brewers; however, it is also a nuisance in many industrial processes, in clinical settings, and in the laboratory. Chemostat-based evolution experiments are impaired by inadvertent selection for aggregation, which we observe in 35% of populations. These populations provide a testing ground for understanding the breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and which of those mechanisms provide the biggest adaptive advantages. In this study, we employed experimental evolution as a tool to ask whether one or many routes to flocculation are favored, and to engineer a strain with reduced flocculation potential. Using a combination of whole genome sequencing and bulk segregant analysis, we identified causal mutations in 23 independent clones that had evolved cell aggregation during hundreds of generations of chemostat growth. In 12 of those clones, we identified a transposable element insertion in the promoter region of known flocculation gene FLO1, and, in an additional five clones, we recovered loss-of-function mutations in transcriptional repressor TUP1, which regulates FLO1 and other related genes. Other causal mutations were found in genes that have not been previously connected to flocculation. Evolving a flo1 deletion strain revealed that this single deletion reduces flocculation occurrences to 3%, and demonstrated the efficacy of using experimental evolution as a tool to identify and eliminate the primary adaptive routes for undesirable traits.

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Crystal structure of the WOPR-DNA complex and implications for Wor1 function in white-opaque switching of Candida albicans

Cited by 16 publications

References 37 publications

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

SUMOylation of Wor1 by a novel SUMO E3 ligase controls cell fate in Candida albicans

Experimental evolution reveals favored adaptive routes to cell aggregation in yeast

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