Promoter inactivation or inhibition by sequence-specific methylation and mechanisms of reactivation

Walter Doerfler, Arnd Hoeveler, Bernd Weisshaar, Pawel Dobrzanski, Dagmar Knebel, Klaus Dieter Langner, Sabine Achten, Ulrich Müller

Research output: Contribution to journalArticlepeer-review

Abstract

In studies on adenovirus promoters, predominantly on the late E2A promoter of adenovirus type 2 (Ad2), we have demonstrated by a number of experimental approaches that the sequence-specific methylation of three 5′-CCGG-3′ sequences inactivates this promoter. Recently, we have developed a cell-free transcription system in which the methylation-inactivation of eukaryotic promoters can be studied in detail. It has also been shown that methylation-caused promoter inactivation can be reversed by the 289 amino acid E1A protein of Ad2 or of adenovirus type 5. In the presence of this protein with a transactivating effect, transcription is initiated at the authentic cap site of the methylated late E2A promoter. A similar reactivation of the methylated late E2A promoter can also be effected by a cis-acting genetic element, i.e., the strong enhancer of human cytomegalovirus. Further studies will be directed toward the biochemical mechanisms of promoter silencing by sequence-specific methylations.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalCell Biophysics
Volume15
Issue number1-2
DOIs
StatePublished - Aug 1 1989
Externally publishedYes

Keywords

  • Adenovirus promoter
  • E1A protein of adenovirus type 2
  • adenovirus type 2
  • cell-free transcription system
  • enhancer of human cytomegalovirus
  • human cytomegalovirus
  • promoter methylation and gene inactivation
  • reactivation of methylation-inhibited promoter

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology

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