1. HOW ARE CHROMATIN STATES PROPAGATED THROUGH DNA REPLICATION? During DNA replication, chromatin–based regulatory information faces two challenges, the disruption caused by passage of the replication machinery, and the two-fold increase in DNA. We aim to understand how of these challenges are met in the PcG system by reconstituting propagation of chromatin states through DNA replication. Current projects involve analyzing the behaviour of both PcG proteins and histones during DNA replication, and how chromatin structure is restored after DNA replication.
2. HOW ARE CHROMATIN STATES PROPAGATED THROUGH MITOSIS? For transcription states to be preserved through cell division, chromatin structures must also survive mitosis, when chromosome structure is altered and many factors are released from chromosomes. We recently identified two classes of PcG protein binding sites in Drosophila cells, one of which retains PcG proteins in mitosis. The features of the sites that persist in mitosis suggest they could have a role in higher order organization of chromatin. Current work aims to determine how and why PcG proteins are lost from some sites in mitosis but not others. Specifically we are interested in the chromatin structure of both types of sites in interphase and mitosis, and how PcG proteins are recruited to them. We also aim to test the idea that retained PcG proteins at some sites facilitate reloading of PcG proteins at other sites and restoration of long range interactions among PcG bound sites. Finally, we are also investigating PcG-interacting proteins that are enriched in mitosis.