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1,25-dihydroxyvitamin D inhibits human ANP gene promoter activity

Songcang Chen1, Karl Nakamura, David G Gardner

  • 1Diabetes Center and Department of Medicine, University of California at San Francisco, 94143-0540, USA.

Regulatory Peptides
|April 20, 2005
PubMed

Insights

The vitamin D receptor (VDR) suppresses the atrial natriuretic peptide (ANP) gene in heart cells. This inhibition occurs through protein interactions, not direct DNA binding, within a specific promoter region.

Area of Science:

  • Cardiovascular Biology
  • Molecular Endocrinology
  • Gene Regulation

Background:

  • 1,25-dihydroxyvitamin D and its nuclear receptor (VDR) influence cardiovascular and renal systems.
  • Liganded VDR previously shown to inhibit cardiac myocyte hypertrophy and related gene expression.

Purpose of the Study:

  • To confirm VDR-mediated suppression of the human ANP gene promoter.
  • To identify the specific promoter region and mechanism involved in VDR-dependent suppression.

Main Methods:

  • Confirmation of VDR-mediated suppression using time-, ligand-, and retinoid X receptor-dependent assays.
  • Deletion analysis to pinpoint the critical promoter region (-217 to -104).
  • Mutation analysis of CArG elements within the promoter region.

Main Results:

  • VDR-dependent suppression of the human ANP gene promoter was confirmed.
  • A promoter region between -217 and -104 was essential for VDR-mediated suppression.
  • Mutation of CArG elements did not abolish the suppression effect.
  • Direct binding of liganded VDR to the -217 to -104 region was not observed.

Conclusions:

  • VDR-mediated suppression of the ANP gene promoter is confirmed.
  • The critical regulatory region for VDR suppression is located between -217 and -104.
  • VDR likely inhibits ANP gene expression through protein-protein interactions with transcription factors, rather than direct DNA binding.

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