Figure 10. Epigenetic silencing pathway for the p16-Arf-p15 locus.

Gene repression pressure leads to recruitment of EZH2-containing Polycomb repressive complex-2 (PRC2) to the transcription complex, that trimethylates H3K27 and thus initiates the repression. The PRC2-related repression is reversible under condition of transcription pressure. However, in the case of long-term silence, Polycomb repressive complex-1 (PRC1) is recruited to the PRC2-repressed genes and activates H3K9 trimethylation subsequently, which may subsequently induce DNA methylation and chromatin remodeling with assistance of other silencers including DNMTs, HDACs, and heterochromatin binding protein HP1. The content within the yellow dash-square presents the discovery in the present study that connects two epigenetic landmarks the PRC1 binding and H3K9 trimethylation together.