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CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene

Academic Article
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Overview

authors

  • Ohtanifujita, N.
  • Fujita, T.
  • Aoike, A.
  • Osifchin, N. E.
  • Robbins, Paul D.
  • Sakai, T.

publication date

  • 1993

journal

  • Oncogene  Journal

abstract

  • Cytosine methylation of CpG sites in the promoter region of eucaryotic genes is involved in the inactivation of expression of certain genes. Given that methylation can lead to reduced transcription, it is possible that expression of tumor-suppressor genes is also inactivated by hypermethylation, thereby contributing to the etiology of cancer. Recently we found five sporadic retinoblastoma tumors (16% of all unilateral cases) with hypermethylation of the 5' end of the retinoblastoma gene without detecting any structural abnormalities. However, it is unclear whether the promoter of the retinoblastoma gene is actually inactivated by its hypermethylation. Here we show that specific hypermethylation in the promoter region of the retinoblastoma gene reduces its expression to only 8% of the unmethylated control. Furthermore, we have found that two transcription factors important for the promoter activity, an activating transcription factor (ATF)-like factor and the retinoblastoma binding factor 1, do not bind when their recognition sequences are CpG methylated. These results in vitro strongly support the hypothesis that CpG methylation of the human tumor-suppressor gene can result in the inactivation of the gene and thus lead to oncogenesis.

subject areas

  • 5-Methylcytosine
  • Base Sequence
  • Cell Line
  • Consensus Sequence
  • Cytosine
  • Gene Expression
  • Genes, Retinoblastoma
  • Humans
  • In Vitro Techniques
  • Methylation
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Retinoblastoma Protein
  • Transcription Factors
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Identity

International Standard Serial Number (ISSN)

  • 0950-9232

PubMed ID

  • 8455933
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Additional Document Info

start page

  • 1063

end page

  • 1067

volume

  • 8

issue

  • 4

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