Inheritance through DNA Replication
During DNA replication, chromatin structure is disrupted (1), and the DNA is completely unwound. This can alter transcription complexes present on the DNA in vitro (2) and can lead to reprogramming of gene expression (e.g.3). Inheritance through DNA replication faces two challenges: surviving or recovering from the physical disruption caused by passage of a DNA replication fork; and the two-fold increase in the amount of DNA.
Three models for how PcG proteins meet the first challenge can be envisioned. Model 1 suggests that PcG proteins remain associated with chromatin and are inherited to the daughter strands. One way this could occur is if PcG proteins interact with multiple nucleosomes so that their interactions are only partially disrupted by the DNA polymerase. Another possibility is that PcG proteins may recognize single stranded (unwound) DNA by PcG proteins (4). A second version of this model suggests PcG proteins are maintained on chromatin during passage of the DNA polymerase by interactions between PcG proteins and the replication machinery. There is precedence for coordination of chromatin modification and DNA replication through protein-protein interactions (5-7) Model 2 suggests that PcG proteins create a mark on chromatin that is stable through DNA replication, and subsequently used to recruit PcG proteins and re-establish repression. Methylation of lysine 27 of histone H3 by PRC2, which is specifically recognized by the chromodomain of Polycomb (Pc) (a PRC1 component) is a candidate for such a mark (8, 9). Model 3 posits that replication disrupts PcG complexes, and restoration of repression essentially recapitulates initial targeting by events.
The second challenge is restoring full repression to both daughters. This is generally suggested to involve cooperative interactions among the segregated "parental" complexes and new complexes, but has not been demonstrated for PcG proteins. It might also involve interactions between the two newly replicated daughters, and proteins like cohesins that can mediate such interactions.
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