DNA Methylation: A Defense Mechanism Against the Expression of Foreign DNA?

  • W. Doerfler

Abstract

Over the past 16 years, my laboratory has studied several aspects of DNA methylation in mammalian cells. For much of the analytical work, we have used the system of human adenoviruses, in particular integrated adenovirus genomes in adenovirus-induced tumor cells or in adenovirus type 12 (Ad12)-transformed cells. Since cell lines propagated in culture and adenovirus genomes as foreign DNA in mammalian cells could be considered to present very special experimental situations, we have also analyzed patterns of DNA methylation in a number of endogenous human gene or DNA segments in primary human white blood cells and in human malignancies or cell lines derived from them. Our major contributions to the field of DNA methylation have been the following:
  1. 1)

    The demonstration that foreign DNA integrated into the mammalian genome becomes de novo methylated in very specific patterns and in an apparently specific temporal sequence [34, 35, 42, 44–46].

     
  2. 2)

    The sequence-specific methylation of viral promoters in mammalian or insect cells leads to the inhibition or inactivation of these promoters [5, 29, 33, 37–39, 41, 50, 51]. This inhibition is probably due to the interference with the interaction of cellular transcription factors with viral promoter motifs [24–26].

     
  3. 3)

    This inhibition is not unconditional, but can be overcome by the 289 amino acid E1A protein of adenovirus type 2 (Ad2) [38, 51], a paradigm transactivator [19], or by a strong viral enhancer [30].

     
  4. 4)

    De novo patterns of DNA methylation can be generated by the gradual spreading of DNA methylation [34, 35, 39, 42, 47, 48]. The spreading of DNA methylation appears to be influenced by proteins bound to specific segments of DNA, but can, in turn, affect the stability of DNA-protein complexes.

     

Keywords

Lymphoma Leukemia Recombination Interferon Lution 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • W. Doerfler
    • 1
  1. 1.Institut für GenetikUniversität KölnKöln 41Germany

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