Figure 5.

Model for the molecular mechanism of gene silencing mediated by DNA methylation of transcribed regions of a gene. (a) Before de novo methylation (at the blastocyst stage), EF1α and (maybe) the reporter gene are unmethylated. (b) During de novo methylation by the Dnmts, the reporter gene is methylated as it does not correspond to a protectable CpG-rich island. In contrast, the EF1α CpG-rich island is protected from methylation as it is in a special chromatin structure (the waves). (c) The partners of Dnmts and MBD induce a change of chromatin structure in EF1α (the modified waves). This may be involving methylated histones and/or HP1. (d) This change of chromatin structure interferes in part with the protection of the EF1α CpG-rich against CpG methylation. The degree of the interference is in relation with the density of methylation of the reporter gene (compare LacZ and LagZ [β-gal⁺]). (e) Chromatin conformation and transcription of the transgene in somatic tissue.