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Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
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Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

Role of DNA 5-methylcytosine transferase in cell transformation by fos

A V Bakin1, T Curran

  • 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Science (New York, N.Y.)
|January 15, 1999
PubMed

Insights

The Fos oncoprotein transforms cells by increasing DNA methylation and histone deacetylation. Inhibiting these processes, specifically DNA methyltransferase 1 (dnmt1), reverses Fos-induced cell transformation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Fos and Jun oncoproteins form dimers that activate transcription via activator protein-1 (AP-1) sites.
  • Cellular transformation by oncogenes can involve epigenetic modifications.
  • DNA methylation and histone deacetylation are key epigenetic regulatory mechanisms.

Purpose of the Study:

  • To investigate the role of DNA methylation and histone deacetylation in Fos-mediated cellular transformation.
  • To determine if alterations in DNA methyltransferase 1 (dnmt1) expression are associated with Fos transformation.
  • To explore the therapeutic potential of targeting epigenetic modifications in Fos-transformed cells.

Main Methods:

  • Representational difference analysis (RDA) to compare gene expression between normal and Fos-transformed fibroblasts.
  • Quantitative analysis of 5-methylcytosine levels in cellular DNA.
  • Transfection assays to introduce the Dnmt1 gene.
  • Inhibition studies targeting dnmt1 expression/activity and histone deacetylase (HDAC).

Main Results:

  • Fos-transformed cells exhibited a threefold increase in DNA 5-methylcytosine transferase (dnmt1) expression compared to normal fibroblasts.
  • Fos-transformed cells showed approximately 20% higher 5-methylcytosine content in their DNA.
  • Overexpression of Dnmt1 induced morphological transformation, mimicking Fos transformation.
  • Inhibition of dnmt1 or histone deacetylase activity led to the reversion of Fos-induced cell transformation.

Conclusions:

  • Fos-mediated cellular transformation appears to be driven by epigenetic alterations, specifically increased DNA methylation and histone deacetylation.
  • DNA methyltransferase 1 (dnmt1) plays a critical role in the transformation process induced by Fos.
  • Targeting epigenetic regulators like dnmt1 and HDACs offers a potential therapeutic strategy against Fos-driven cancers.

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