The Hsp90 Molecular Chaperone Regulates the Transcription Factor Network Controlling Chromatin Accessibility

Zlata Gvozdenov, Lindsey D. Bendix, Janhavi Kolhe, Brian C. Freeman

Research output: Contribution to journalArticle

Abstract

Genomic events including gene regulation and chromatin status are controlled by transcription factors. Here we report that the Hsp90 molecular chaperone broadly regulates the transcription factor protein family. Our studies identified a biphasic use of Hsp90 in which early inactivation (15 min) of the chaperone triggered a wide reduction of DNA binding events along the genome with concurrent changes to chromatin structure. Long-term loss (6 h) of Hsp90 resulted in a decline of a divergent yet overlaying pool of transcription factors that produced a distinct chromatin pattern. Although both phases involve protein folding, the early point correlated with Hsp90 acting in a late folding step that is critical for DNA binding function, whereas prolonged Hsp90 inactivation led to a significant decrease in the steady-state transcription factor protein levels. Intriguingly, despite the broad chaperone impact on a variety of transcription factors, the operational influence of Hsp90 was at the level of chromatin with only a mild effect on gene regulation. Thus, Hsp90 selectively governs the transcription factor process overseeing local chromatin structure.

Original languageEnglish (US)
Pages (from-to)4993-5003
Number of pages11
JournalJournal of Molecular Biology
Volume431
Issue number24
DOIs
StatePublished - Dec 6 2019

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Keywords

  • Chromatin
  • Hsp90
  • Molecular chaperone
  • Transcription factor

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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