PlumX Metrics
Embed PlumX Metrics

Silencing of the Mouse H-rev107 Gene Encoding a Class II Tumor Suppressor by CpG Methylation *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 277, Issue: 34, Page: 30543-30550
2002
  • 20
    Citations
  • 0
    Usage
  • 16
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

H-rev107 is a tumor suppressor originally isolated in revertants of H- ras -transformed cell lines. The gene is ubiquitously expressed in normal tissues but down-regulated in primary carcinomas or in many cell lines derived from tumors, including WEHI 7.1 lymphoma cells. Here, we show that unlike in H-rev107 -expressing cells or tissues the 5′-end of H-rev107 containing a CpG-rich region of 421 bp is highly methylated in WEHI 7.1 lymphoma cells, correlating with silencing of this gene. Repression of H-rev107 transcription in these cells could be relieved by chemically induced hypomethylation with 5-aza-dC. In addition, upon in vitro methylation, expression of the luciferase reporter gene driven by the H-rev107 promoter decreased by 80% in WEHI 7.1 and 293 cells. Furthermore, co-transfection of the methyl-CpG binding proteins, MeCP2 and MBD2, inhibited H-rev107 promoter activity up to 70% in SL2 cells when the promoter was methylated. By chromatin immunoprecipitation assays, we observed in vivo binding of MeCP2 and MBD2 to the 5′-end of H-rev107 in WEHI 7.1 cells, which was reduced to undetectable levels upon 5-aza-dC treatment, concluding that MeCP2 and MBD2 might be involved in silencing the methylated H-rev107 gene in lymphoma cells and probably certain tumors.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know