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Androgen receptor complexes probe DNA for recognition sequences by short random interactions.

Martin E Van Royen1, Wiggert A van Cappellen, Bart Geverts

  • 1Department of Pathology, Erasmus MC, 3000 CA Rotterdam, The Netherlands.

Journal of Cell Science
|February 1, 2014
PubMed
Summary

Researchers developed a quantitative model for transcription factor action using androgen receptor (AR) dynamics. They identified distinct AR-DNA binding events and hormone-induced complex formation, revealing how transcription factors interact with DNA.

Keywords:
DNA bindingFCSFRAPSingle-molecule microscopySteroid ReceptorTranscription factor

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biophysics

Background:

  • Advances in live-cell imaging have improved understanding of transcription factor dynamics.
  • A quantitative framework for transcription factor action is still needed.

Purpose of the Study:

  • To develop a quantitative model for transcription factor action using the androgen receptor (AR) as a model.
  • To characterize AR-DNA binding kinetics and hormone-induced complex formation.

Main Methods:

  • Utilized single-molecule microscopy, photobleaching, and correlation spectroscopy.
  • Applied these fluorescence microscopy techniques to study AR in living cells.

Main Results:

  • Distinguished two types of AR-DNA binding: brief (milliseconds) and hormone-induced longer-lasting (seconds).
  • Observed hormone-induced slowing of AR mobility, indicating large co-regulator complex formation.
  • Proposed a model of transcription factor-DNA interaction.

Conclusions:

  • Mobile, hormone-induced transcription factor complexes transiently probe DNA at random sites.
  • Stable transcription initiation complexes form only upon binding to specific DNA recognition sequences.