Effect of DNA methylation on the binding of vertebrate and plant proteins to DNA

Abstract

Many studies have shown correlations between increased gene expression and decreased DNA methylation (e.g., Sullivan et al., 1989; Piva et al., 1989; Shinar et al., 1989; Jahroudi et al., 1990; Burbelo et al., 1990). The demethylation associated with gene expression has been found either in localized sites or in extensive regions. When the tissue-specific demethylation is localized, it may be in the upstream regulatory regions, at the 5′ end of the gene, in an intron, or in the 3′ flanking region of the gene (Jump et al., 1987; Broad et al., 1989; Lamson and Stockdale, 1989; Umeno et al., 1988; Sullivan et al., 1989). Sometimes the localized demethylation occurring before or concomitantly with the activation of transcription is followed by a more generalized demethylation of the gene region (Umeno et al., 1988; Sullivan et al., 1989; Blackman and Koshland, 1985; Toth et al., 1989). In other cases, all the detected demethylation occurred before or concurrently with the onset of transcription (Lamson and Stockdale, 1989; Benvenisty et al., 1985; Saluz et al., 1988). However, for some genes, the demethylation associated with the activation of transcription was detected only after the turn on of the gene (Lock et al., 1987; Enver et al., 1988). In the latter cases, DNA methylation may just help keep a switched-off gene region silent. Another possibility is that the demethylation of critical mCpGs that preceded the turn on of transcription may have been missed because only a small fraction of CpG sites in the gene region (usually only 5′-CCGG-3′ [HpaII] or 5′-GCGC-3′ [HhaI] sites) were studied.