Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity.
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.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Motoko
M
Unoki
Yusuke
Y
Nakamura
D001483:Base Sequence; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D051767:Early Growth Response Protein 2; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D014157:Transcription Factors