PMID- 14596916 OWN - NLM STAT- MEDLINE DCOM- 20031223 LR - 20190621 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 554 IP - 1-2 DP - 2003 Nov 6 TI - Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity. PG - 67-72 AB - 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. FAU - Unoki, Motoko AU - Unoki M AD - 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. FAU - Nakamura, Yusuke AU - Nakamura Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (DNA-Binding Proteins) RN - 0 (EGR2 protein, human) RN - 0 (Early Growth Response Protein 2) RN - 0 (Transcription Factors) SB - IM MH - Base Sequence MH - Cell Line, Tumor MH - CpG Islands/*physiology MH - *DNA Methylation MH - DNA-Binding Proteins/*genetics MH - Down-Regulation MH - Early Growth Response Protein 2 MH - Enhancer Elements, Genetic/*genetics MH - Gene Expression Regulation, Neoplastic MH - Genes, Reporter MH - Humans MH - Introns/*genetics MH - Molecular Sequence Data MH - Sequence Analysis, DNA/methods MH - Transcription Factors/*genetics EDAT- 2003/11/05 05:00 MHDA- 2003/12/24 05:00 CRDT- 2003/11/05 05:00 PHST- 2003/11/05 05:00 [pubmed] PHST- 2003/12/24 05:00 [medline] PHST- 2003/11/05 05:00 [entrez] AID - S0014579303010925 [pii] AID - 10.1016/s0014-5793(03)01092-5 [doi] PST - ppublish SO - FEBS Lett. 2003 Nov 6;554(1-2):67-72. doi: 10.1016/s0014-5793(03)01092-5.