Promoter characterization of Semaphorin SEMA3F, a tumor suppressor gene

Sophie Kusy, Vincent Potiron, Chan Zeng, Wilbur Franklin, Elisabeth Brambilla, John Minna, Harry A. Drabkin, Joëlle Roche

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The tumor suppressor gene, Semaphorin SEMA3F, is frequently downregulated in lung cancer. Understanding the specific mechanism of SEMA3F suppression should be informative in terms of epithelial carcinogenesis and potential therapeutic interventions. Although a CpG-island is located 5083-3927 nt upstream of the translation start site, there have been no previous reports dealing with SEMA3F promoter regulation. We have now mapped the transcriptional initiation sites within the CpG-island and defined the region necessary for transcriptional activation. We then looked for evidence of SEMA3F promoter methylation since SEMA3F mutations are rare. By Southern blot and methylation-specific PCR assays, we identified a region in cell lines (i.e., area d at position minus 3850-3644 nt) for which methylation was significantly (P < 0.0001) correlated with loss of expression. However, histone deacetylase inhibition with Trichostatin A was much more effective than 5-aza-2′-deoxycytidine in stimulating SEMA3F. Our results suggest that while SEMA3F promoter methylation correlates with repression, chromatin remodeling through histone deacetylase inhibition is sufficient to activate SEMA3F expression.

Original languageEnglish (US)
Pages (from-to)66-76
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1730
Issue number1
DOIs
StatePublished - Jul 25 2005

Keywords

  • Epigenetic modifications
  • Lung cancer
  • Reporter gene
  • Semaphorin SEMA3F promoter
  • Transcriptional initiation site

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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