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A DNA sequence directed mutual transcription regulation of HSF1 and NFIX involves novel heat sensitive protein

Umashankar Singh1, Erik Bongcam-Rudloff, Bengt Westermark

  • 1Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. umashankar.singh@genpat.uu.se

Plos One
|April 2, 2009
PubMed
Abstract

Insights

Nuclear factor 1 (NFIX) and heat shock factor 1 (HSF1) mutually regulate each other's transcription. This interaction is heat shock sensitive and involves specific DNA sequences, offering new insights into stress-induced gene regulation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Biology

Background:

  • Nuclear factor 1 (NFIX) is implicated in PDGFB-induced glioblastoma, but its mechanisms are unknown.
  • Heat shock factor 1 (HSF1) influences carcinogenesis, yet its transcriptional control remains elusive.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating HSF1 transcription.
  • To investigate the interplay between NFIX and HSF1 in gene regulation.

Main Methods:

  • Microarray expression profiling
  • Yeast-two-hybrid screening
  • Analysis of protein-DNA interactions and subcellular localization.

Main Results:

  • NFIX, CGGBP1, and HMGN1 interaction regulates HSF1 expression via CGG repeats in the HSF1 promoter.
  • Heat shock induces NFIX recruitment to the HSF1 promoter, altering DNA binding.
  • HSF1 represses NFIX expression through its promoter in a heat shock-sensitive manner.

Conclusions:

  • NFIX and HSF1 exhibit reciprocal transcriptional repression dependent on promoter-specific DNA sequences.
  • A novel mechanism of heat shock-sensitive, DNA sequence-directed transcriptional regulation between NFIX and HSF1 is identified.
  • Findings provide new insights into transcriptional regulation under cellular stress conditions.

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