The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and...

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Autores principales:	Faiza Tebbji, Yaolin Chen, Adnane Sellam, Malcolm Whiteway
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Candida albicans SWI/SNF complex carbon utilization genomic occupancy morphogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/42222f64589b4bcc8b978645487356dd
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spelling	oai:doaj.org-article:42222f64589b4bcc8b978645487356dd2021-11-15T15:21:53ZThe Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mSphere.00497-172379-5042https://doaj.org/article/42222f64589b4bcc8b978645487356dd2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00497-17https://doaj.org/toc/2379-5042ABSTRACT SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits. The role of Snf6 in C. albicans was investigated by determining its genome-wide occupancy using chromatin immunoprecipitation coupled to tiling arrays in addition to transcriptional profiling of the snf6 conditional mutant. Snf6 directs targets that were enriched in functions related to carbohydrate and amino acid metabolic circuits, to cellular transport, and to heat stress responses. Under hypha-promoting conditions, Snf6 expanded its set of targets to include promoters of genes related to respiration, ribosome biogenesis, mating, and vesicle transport. In accordance with the genomic occupancy data, an snf6 doxycycline-repressible mutant exhibited growth defects in response to heat stress and also when grown in the presence of different fermentable and nonfermentable carbon sources. Snf6 was also required to differentiate invasive hyphae in response to different cues. This study represents the first comprehensive characterization, at the genomic level, of the role of SWI/SNF in the pathogenic yeast C. albicans and uncovers functions that are essential for fungal morphogenesis and metabolic flexibility. IMPORTANCE Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections in immunosuppressed patients. Current therapeutics include a limited number of molecules that suffer from limitations, including growing clinical resistance and toxicity. New molecules are being clinically investigated; however, the majority of these potential antifungals target the same processes as do the standard antifungals and might confront the same problems of toxicity and loss of efficiency due to the common resistance mechanisms. Here, we characterized the role of Snf6, a fungus-specific subunit of the chromatin-remodeling complex SWI/SNF. Our genomic and phenotypic data demonstrated a central role of Snf6 in biological processes that are critical for a fungal pathogen to colonize its host and cause disease, suggesting Snf6 as a possible antifungal target.Faiza TebbjiYaolin ChenAdnane SellamMalcolm WhitewayAmerican Society for MicrobiologyarticleCandida albicansSWI/SNF complexcarbon utilizationgenomic occupancymorphogenesisMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans SWI/SNF complex carbon utilization genomic occupancy morphogenesis Microbiology QR1-502
spellingShingle	Candida albicans SWI/SNF complex carbon utilization genomic occupancy morphogenesis Microbiology QR1-502 Faiza Tebbji Yaolin Chen Adnane Sellam Malcolm Whiteway The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits. The role of Snf6 in C. albicans was investigated by determining its genome-wide occupancy using chromatin immunoprecipitation coupled to tiling arrays in addition to transcriptional profiling of the snf6 conditional mutant. Snf6 directs targets that were enriched in functions related to carbohydrate and amino acid metabolic circuits, to cellular transport, and to heat stress responses. Under hypha-promoting conditions, Snf6 expanded its set of targets to include promoters of genes related to respiration, ribosome biogenesis, mating, and vesicle transport. In accordance with the genomic occupancy data, an snf6 doxycycline-repressible mutant exhibited growth defects in response to heat stress and also when grown in the presence of different fermentable and nonfermentable carbon sources. Snf6 was also required to differentiate invasive hyphae in response to different cues. This study represents the first comprehensive characterization, at the genomic level, of the role of SWI/SNF in the pathogenic yeast C. albicans and uncovers functions that are essential for fungal morphogenesis and metabolic flexibility. IMPORTANCE Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections in immunosuppressed patients. Current therapeutics include a limited number of molecules that suffer from limitations, including growing clinical resistance and toxicity. New molecules are being clinically investigated; however, the majority of these potential antifungals target the same processes as do the standard antifungals and might confront the same problems of toxicity and loss of efficiency due to the common resistance mechanisms. Here, we characterized the role of Snf6, a fungus-specific subunit of the chromatin-remodeling complex SWI/SNF. Our genomic and phenotypic data demonstrated a central role of Snf6 in biological processes that are critical for a fungal pathogen to colonize its host and cause disease, suggesting Snf6 as a possible antifungal target.
format	article
author	Faiza Tebbji Yaolin Chen Adnane Sellam Malcolm Whiteway
author_facet	Faiza Tebbji Yaolin Chen Adnane Sellam Malcolm Whiteway
author_sort	Faiza Tebbji
title	The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
title_short	The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
title_full	The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	genomic landscape of the fungus-specific swi/snf complex subunit, snf6, in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/42222f64589b4bcc8b978645487356dd
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The Genomic Landscape of the Fungus-Specific SWI/SNF Complex Subunit, Snf6, in <named-content content-type="genus-species">Candida albicans</named-content>

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