Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants

J DeRisi1, B van den Hazel, P Marc

  • 1Howard Hughes Medical Institute and Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5428, USA.

FEBS Letters
|March 29, 2000
PubMed

Insights

Researchers identified 26 gene targets of transcription factors Pdr1p and Pdr3p in yeast, revealing new roles in cell defense and biosynthesis. Some gene expressions were unexpectedly repressed, highlighting complex regulatory roles.

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Transcription Factor Regulation

Background:

  • Pdr1p and Pdr3p are homologous transcription factors in Saccharomyces cerevisiae.
  • Understanding their regulatory targets is crucial for deciphering cellular responses to stress and drug resistance.

Purpose of the Study:

  • To identify novel target genes regulated by activated mutants of Pdr1p and Pdr3p.
  • To investigate the functional roles of these targets in yeast.
  • To compare the regulatory roles of Pdr1p and Pdr3p.

Main Methods:

  • Screening of Saccharomyces cerevisiae complete genome DNA microarrays using cDNA from activated Pdr1p and Pdr3p mutants.
  • Identification and analysis of overexpressed and repressed genes.

Main Results:

  • Identified 26 overexpressed target genes, with 21 being novel, many of unknown function.
  • These targets are involved in transport, membrane lipid, and cell wall biosynthesis, and cellular defense against stress.
  • Unexpectedly, the expression of 23 other genes was repressed in the mutants.
  • Pdr1p and Pdr3p exhibit distinct regulatory patterns on their targets.
  • Repressed genes lacked known pleiotropic drug resistance binding sites in their promoters.

Conclusions:

  • Pdr1p and Pdr3p regulate a diverse set of genes involved in fundamental cellular processes and stress response.
  • The identification of novel targets expands our understanding of yeast transcriptional regulation.
  • The distinct and repressed gene expression patterns suggest complex regulatory mechanisms beyond simple activation.