Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5

Motohiko Oshima, Junsei Mimura, Masayuki Yamamoto, Yoshiaki Fujii-Kuriyama

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The Aryl hydrocarbon receptor repressor (AhRR) has been proposed to inhibit Aryl hydrocarbon receptor (AhR) activity by competing with AhR for forming a heterodimer with AhR nuclear translocator (Arnt) and subsequently binding to the xenobiotic responsive elements (XRE). However, the precise mechanism of AhRR inhibitory activity remains unknown. Analysis of the inhibitory activity of AhRR on the expression of a TK promoter-driven reporter has localized a core repressor domain in the sequence of amino acid residue 555-701. The inhibitory activity of AhRR is sensitive to a histone deacetylase (HDAC) inhibitor, trichostatin A. By using the yeast two-hybrid screening method with the C-terminal sequence of AhRR as bait, we identified a binding partner, Ankyrin-repeat protein2 (ANKRA2), a protein known to interact with HDAC4 and HDAC5. RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR. We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors.

Original languageEnglish
Pages (from-to)276-282
Number of pages7
JournalBiochemical and biophysical research communications
Volume364
Issue number2
DOIs
Publication statusPublished - 2007 Dec 14
Externally publishedYes

Keywords

  • ANKRA2
  • AhR repressor (AhRR)
  • Aryl hydrocarbon receptor (AhR)
  • CYP1A1
  • HDAC4
  • HDAC5
  • RFXANK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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