Epigenetic regulation of replication origins

Replication origin density of Xenopus laevis embryonic cells is higher than somatic ones. This ensures rapid and accurate genome duplication during embryonic cell divisions. Close to the mid-blastula transition (MBT), the density of replication origins reverts to the somatic one, initiation of DNA replication becomes restricted to specific sites and correlates with cell cycle lengthening. Intriguingly, in nuclear transfer experiments exposure of somatic nuclei to egg cytoplasm is sufficient to convert the somatic origin density to the embryonic one, suggesting that the replication origin assembly in somatic cells is restrained by epigenetic factors modifiable by the egg cytoplasm. we performed extensive biochemical fraction of egg cytoplasm to identify factors that regulate replication origin density in embryonic and somatic nuclei. this effort led to the isolation of SSRP1 as major factor that stimulates somatic nuclei replication in egg extract. we showed that exposure of somatic nuclei to SSRP1 removes epigenetic determinants that restrain replication origin assembly and restores replication origin density typical of embryonic nuclei on somatic chromatin. Strikingly, SSRP1-mediated regulation of replication origin assembly has a dramatic impact on cell cycle progression and early embryonic development. These results and their implications will be described in details in the context of more general regulation of DNA replication of vertebrate organisms.