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Next Generation Sequencing of DIO intestine DMSO vs NCT (HNF4a agonist)

ABSTRACT: Mice rendered obese with high fat diet were treated by IP injection with N-trans caffeoyltyramine (NCT) (200 mg/kg bid) for 14 days, followed by harvesting of the intestine for analysis, including RNA isolation.

ORGANISM(S): Mus musculus

PROVIDER: GSE178435 | GEO | 2021/06/18

REPOSITORIES: GEO

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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.

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