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

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

PROVIDER: PRJNA533304 | ENA |

REPOSITORIES: ENA

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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 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 [RNA-seq]

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

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-31 | GSE133491 | GEO

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

Project description: Not available

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TAp73 is a master regulator of airway multiciliogenesis

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Monitoring the mating-type-driven transcriptomes of Aspergillus fumigatus

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HMGA1: A master regulator of tumor progression in triple-negative breast cancer cells

Project description:Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231) by reprogramming cancer cells to a stem-like state. We discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy. HMGA1 was knocked-down in MDA-MB-231 cells using siRNA as we previously described (Tesfaye A 2007). RNA from three independent knockdown experiements along with 3 control populations were collected by Rneasy miniprep (Qiagen) and analyzed by Affymetrix Human Exon 1.0 ST platform.

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Identification of a master regulator of differentiation in Toxoplasma

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