A model for the maintenance of chromatin silencing. (a) Replication-coupled maintenance of a silent region of chromatin. Solid lines indicate DNA; cylinders represent nucleosomes (light, old; dark, newly added); circles represent other proteins or protein complexes; flags indicate histone methylation; M indicates DNA methylation (with new methylation in bold); the large oval represents DNA polymerase. Before replication (1), a silenced region is marked by histone methylation and DNA methylation on CG and CNG motifs. As the polymerase moves along the leading strand from left to right (2), methylation on CG dinucleotides is passively maintained behind the replication fork by MET1 (3). Old nucleosomes are randomly distributed between the two chromatids and new nucleosomes are added by the CAF1 chaperone complex (4). In the top chromatid in the diagram (A), there are two adjacent nucleosomes that are methylated on H3 K9, thus providing cues for CAF1 to deposit a new nucleosome that is methylated on H3 K9 by KYP (5). On the bottom chromatid (B), however, the nucleosome distribution leads to loss of epigenetic information at the edge of the silent domain, so new nucleosomes are deposited by CAF1 without H3 K9 methylation (6). CMT3 is therefore able to use the cues provided by H3 K9 methylation to properly maintain CNG methylation on the top chromatid (7), but not the bottom (8). Chromatin remodeling by DDM1 enables both DNA and histone methylation, perhaps by allowing access of other proteins to the DNA. (b) RNA-based reinforcement of silencing. The bottom (B) chromatid from (a) is shown after the replication fork has passed completely. Now, siRNAs homologous to the silent region guide H3 K9 methylation by KYP and DNA methylation by DRM. H3 K9 methylation also allows the maintenance of CNG methylation by CMT3. The problem shown in (a) is thus solved: the silent domain is fully maintained, despite random nucleosome distribution during replication.
Zilberman and Henikoff Genome Biology 2004 5:249 doi:10.1186/gb-2004-5-12-249