Four mechanisms by which methylation can alter transcription. Methylation may have no effect on expression (top). Methylation-sensitive transcription factors cannot activate a methylated promoter (second pair of panels). Transcriptionally competent promoters with nucleosomes (dark circles) can acquire a protein complex with methylation (third pair of panels). This may include MeCPs and deacetylases, which alter nucleosome function (as shown by quartered circles) resulting in silencing. Some transcription factors require their target sites to be methylated before they can bind and promote gene expression (fourth pair of panels). A hypothetical situation where a repressor is dislodged by methylation (bottom). The last two models could explain the instances of expression from methylated alleles (see text).
