Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5
Journal Article
·
· Biochemical and Biophysical Research Communications
- Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577 (Japan)
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.
- OSTI ID:
- 21033006
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 364; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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