Heat Shock Factor-4 (HSF-4a) Represses Basal Transcription through Interaction with TFIIF

Wojciech Frejtag, Yan Zhang, Rujuan Dai, Mark G. Anderson, Nahid F Mivechi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The heat shock transcription factors (HSFs) regulate the expression of heat shock proteins (hsps), which are critical for normal cellular proliferation and differentiation. One of the HSFs, HSF-4, contains two alternative splice variants, one of which possesses transcriptional repressor properties in vivo. This repressor isoform inhibits basal transcription of hsps 27 and 90 in tissue culture cells. The molecular mechanisms of HSF-4a isoform-mediated transcriptional repression is unknown. Here, we present evidence that HSF-4a inhibits basal transcription in vivo when it is artificially targeted to basal promoters via the DNA-binding domain of the yeast transcription factor, GAL4. By using a highly purified, reconstituted in vitro transcription system, we show that HSF-4a represses basal transcription at an early step during preinitiation complex assembly, as pre-assembled preinitiation complexes are refractory to the inhibitory effect on transcription. This repression occurs by the HSF-4a isoform, but not by the HSF-4b isoform, which we show is capable of activating transcription from a heat shock element-driven promoter in vitro. The repression of basal transcription by HSF-4a occurs through interaction with the basal transcription factor TFIIF. TFIIF interacts with a segment of HSF-4a that is required for the trimerization of HSF-4a, and deletion of this segment no longer inhibits basal transcription. These studies suggest that HSF-4a inhibits basal transcription both in vivo and in vitro. Furthermore, this is the first report identifying an interaction between a transcriptional repressor with the basal transcription factor TFIIF.

Original languageEnglish (US)
Pages (from-to)14685-14694
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number18
DOIs
StatePublished - May 4 2001

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Transcription
Shock
Hot Temperature
Protein Isoforms
heat shock transcription factor
transcription factor TFIIF
HSP27 Heat-Shock Proteins
HSP90 Heat-Shock Proteins
Tissue culture
Heat-Shock Proteins
Refractory materials
Yeast
Transcription Factors
Cell Culture Techniques
Yeasts
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Heat Shock Factor-4 (HSF-4a) Represses Basal Transcription through Interaction with TFIIF. / Frejtag, Wojciech; Zhang, Yan; Dai, Rujuan; Anderson, Mark G.; Mivechi, Nahid F.

In: Journal of Biological Chemistry, Vol. 276, No. 18, 04.05.2001, p. 14685-14694.

Research output: Contribution to journalArticle

Frejtag, Wojciech ; Zhang, Yan ; Dai, Rujuan ; Anderson, Mark G. ; Mivechi, Nahid F. / Heat Shock Factor-4 (HSF-4a) Represses Basal Transcription through Interaction with TFIIF. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 18. pp. 14685-14694.
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