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  • Title: Promoter inactivation or inhibition by sequence-specific methylation and mechanisms of reactivation.
    Author: Doerfler W, Hoeveler A, Weisshaar B, Dobrzanski P, Knebel D, Langner KD, Achten S, Müller U.
    Journal: Cell Biophys; 1989; 15(1-2):21-7. PubMed ID: 2476224.
    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.
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