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The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE133491 | GEO | 2019/12/31

REPOSITORIES: GEO

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The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [ChIP-seq]

Project description:The Negative cofactor 2 (NCT) complex is an evolutionally conserved heterodimeric transcription factor. In Aspergillus fumigatus, the NCT complex consists of two subunits NctA and NctB. Through a genome-wide screening of a transcription factor null mutant strains, we found that loss of the NCT complex leads to a multi-drug resistance phenotype including the azoles (itraconazole, voriconazole and posaconazole) as well as the salvage therapeutic amphotericin B, and terbinafine. To obtain further insight into the molecular mechanisms driving the azole-resistance in the NCT complex null mutants, we analyzed genome-wide binding profiles of NctA using chromatin-immunoprecipitation sequencing (ChIP-seq). Our ChIP-seq analysis revealed that NCT complex binds the promoters of several ergosterol biosynthetic genes, their transcriptional regulators, and the azole efflux pump cdr1B. Taken together, these results suggest that the NCT complex plays a role as a master regulator of drug resistance in A. fumigatus.

2019-12-31 | GSE129967 | GEO

The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [RNA-seq]

Project description:The Negative cofactor 2 (NCT) complex is an evolutionally conserved heterodimeric transcription factor. In Aspergillus fumigatus, the NCT complex consists of two subunits NctA and NctB. Through a genome-wide screening of a transcription factor null mutant strains, we found that loss of the NCT complex leads to a multi-drug resistance phenotype including the azoles (itraconazole, voriconazole and posaconazole) as well as the salvage therapeutic amphotericin B, and terbinafine. To obtain further insight into the molecular mechanisms driving the azole-resistance in the NCT complex null mutants, we analyzed genome-wide gene expression profiles of the nctA and the nctB null mutants using RNA-seq. Our expression profiling revealed that disruption of the genes lead to upregulation of several ergosterol biosynthetic genes, their transcriptional activators, and the azole efflux pump cdr1B. Taken together, these results suggest that the NCT complex plays a role as a master regulator of drug resistance in A. fumigatus.

2019-12-31 | GSE133464 | GEO

The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus.

Project description: Not available

| S-EPMC7194077 | biostudies-literature

The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus

Project description:The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus

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The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [ChIP-seq]

Project description:The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [ChIP-seq]

| PRJNA533304 | ENA

The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [RNA-seq]

Project description:The Negative Cofactor 2 complex is a master regulator of drug resistance in Aspergillus fumigatus [RNA-seq]