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Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans

The pathogenic fungus Candida albicans can undergo phenotypic switching between two heritable states: white and opaque. This phenotypic plasticity facilitates its colonization in distinct host niches. The master regulator WOR1 is exclusively expressed in opaque phase cells. Positive feedback regulat...

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Autores principales: Alkafeef, Selma S., Yu, Clinton, Huang, Lan, Liu, Haoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786334/
https://www.ncbi.nlm.nih.gov/pubmed/29337983
http://dx.doi.org/10.1371/journal.pgen.1007176
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author Alkafeef, Selma S.
Yu, Clinton
Huang, Lan
Liu, Haoping
author_facet Alkafeef, Selma S.
Yu, Clinton
Huang, Lan
Liu, Haoping
author_sort Alkafeef, Selma S.
collection PubMed
description The pathogenic fungus Candida albicans can undergo phenotypic switching between two heritable states: white and opaque. This phenotypic plasticity facilitates its colonization in distinct host niches. The master regulator WOR1 is exclusively expressed in opaque phase cells. Positive feedback regulation by Wor1 on the WOR1 promoter is essential for opaque formation, however the underlying mechanism of how Wor1 functions is not clear. Here, we use tandem affinity purification coupled with mass spectrometry to identify Wor1-interacting proteins. Tup1 and its associated complex proteins are found as the major factors associated with Wor1. Tup1 occupies the same regions of the WOR1 promoter as Wor1 preferentially in opaque cells. Loss of Tup1 is sufficient to induce the opaque phase, even in the absence of Wor1. This is the first such report of a bypass of Wor1 in opaque formation. These genetic analyses suggest that Tup1 is a key repressor of the opaque state, and Wor1 functions via alleviating Tup1 repression at the WOR1 promoter. Opaque cells convert to white en masse at 37°C. We show that this conversion occurs only in the presence of glycolytic carbon sources. The opaque state is stabilized when cells are cultured on non-glycolytic carbon sources, even in a MTLa/α background. We further show that temperature and carbon source affect opaque stability by altering the levels of Wor1 and Tup1 at the WOR1 promoter. We propose that Wor1 and Tup1 form the core regulatory circuit controlling the opaque transcriptional program. This model provides molecular insights on how C. albicans adapts to different host signals to undergo phenotypic switching for colonization in distinct host niches.
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spelling pubmed-57863342018-02-09 Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans Alkafeef, Selma S. Yu, Clinton Huang, Lan Liu, Haoping PLoS Genet Research Article The pathogenic fungus Candida albicans can undergo phenotypic switching between two heritable states: white and opaque. This phenotypic plasticity facilitates its colonization in distinct host niches. The master regulator WOR1 is exclusively expressed in opaque phase cells. Positive feedback regulation by Wor1 on the WOR1 promoter is essential for opaque formation, however the underlying mechanism of how Wor1 functions is not clear. Here, we use tandem affinity purification coupled with mass spectrometry to identify Wor1-interacting proteins. Tup1 and its associated complex proteins are found as the major factors associated with Wor1. Tup1 occupies the same regions of the WOR1 promoter as Wor1 preferentially in opaque cells. Loss of Tup1 is sufficient to induce the opaque phase, even in the absence of Wor1. This is the first such report of a bypass of Wor1 in opaque formation. These genetic analyses suggest that Tup1 is a key repressor of the opaque state, and Wor1 functions via alleviating Tup1 repression at the WOR1 promoter. Opaque cells convert to white en masse at 37°C. We show that this conversion occurs only in the presence of glycolytic carbon sources. The opaque state is stabilized when cells are cultured on non-glycolytic carbon sources, even in a MTLa/α background. We further show that temperature and carbon source affect opaque stability by altering the levels of Wor1 and Tup1 at the WOR1 promoter. We propose that Wor1 and Tup1 form the core regulatory circuit controlling the opaque transcriptional program. This model provides molecular insights on how C. albicans adapts to different host signals to undergo phenotypic switching for colonization in distinct host niches. Public Library of Science 2018-01-16 /pmc/articles/PMC5786334/ /pubmed/29337983 http://dx.doi.org/10.1371/journal.pgen.1007176 Text en © 2018 Alkafeef et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Alkafeef, Selma S.
Yu, Clinton
Huang, Lan
Liu, Haoping
Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title_full Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title_fullStr Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title_full_unstemmed Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title_short Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans
title_sort wor1 establishes opaque cell fate through inhibition of the general co-repressor tup1 in candida albicans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786334/
https://www.ncbi.nlm.nih.gov/pubmed/29337983
http://dx.doi.org/10.1371/journal.pgen.1007176
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