Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity

FEBS Lett. 2003 Nov 6;554(1-2):67-72. doi: 10.1016/s0014-5793(03)01092-5.


We previously demonstrated several lines of evidence indicating that early growth response 2 (EGR2) functions as a tumor suppressor, partly on the basis that its expression was often decreased in human tumors and cancer cell lines. Here we report a possible molecular mechanism to account for down-regulation of EGR2 in tumor cells. Although no genetic mutations in the gene or alterations in methylation status of its promoter were detected, we found a high degree of methylation at CpG islands in intron 1 of EGR2 in cell lines that were expressing this gene at a high level. Moreover, reporter gene experiments revealed that methylated intron 1 had somehow conferred enhancer-like activity. The data imply the existence of a previously unsuspected mechanism of gene expression regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • CpG Islands / physiology*
  • DNA Methylation*
  • DNA-Binding Proteins / genetics*
  • Down-Regulation
  • Early Growth Response Protein 2
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Introns / genetics*
  • Molecular Sequence Data
  • Sequence Analysis, DNA / methods
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Transcription Factors