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Related Experiment Videos

Copper-regulatory domain involved in gene expression

D R Winge1

  • 1Department of Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA.

Progress in Nucleic Acid Research and Molecular Biology
|October 6, 1997
PubMed
Summary

Yeast maintains copper ion homeostasis via transcription factors that bind copper. These factors activate or repress gene expression through distinct mechanisms involving copper cluster formation, ensuring a graded cellular response to environmental copper levels.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Copper ion (Cu(I)) homeostasis is crucial for yeast survival.
  • This balance is achieved through regulated gene expression controlling copper uptake, sequestration, and oxidative stress defense.
  • Cu(I)-sensing transcription factors mediate both positive and negative copper regulation.

Purpose of the Study:

  • To elucidate the distinct mechanisms of Cu(I) regulation in yeast gene expression.
  • To investigate the role of transcription factor structure and copper cluster formation in regulating gene activation and repression.
  • To explore the evolutionary conservation and potential eukaryotic distribution of Cu(I) regulatory domains.

Main Methods:

  • Analysis of Cu(I)-regulated DNA binding in yeast transcription factors Ace1 and Amt1.

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  • Investigation of polycopper cluster formation within regulatory domains.
  • Comparative analysis of transcription factor homologs across different yeast species.
  • Main Results:

    • Cu(I) activation involves stabilized DNA binding via Cu(I) cluster formation in Ace1 and Amt1.
    • Transcription factors are modular, with distinct DNA-binding and activation domains.
    • Cu(I) repression, mediated by Mac1, involves inhibition of the transactivation domain via polycopper thiolate cluster formation.
    • Homologs of the Cu(I) regulatory domain exist in multiple yeast species, suggesting broader eukaryotic relevance.

    Conclusions:

    • Yeast employs distinct Cu(I) regulatory mechanisms for gene activation and repression.
    • Polycopper cluster formation is central to Cu(I) sensing and transcriptional control.
    • The identified Cu(I) regulatory domain is conserved across yeast and potentially other eukaryotes.