Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Mol Cell. 2012 Jun 29;46(6):784-96. doi: 10.1016/j.molcel.2012.05.038.
Epigenetic regulation may involve heritable chromatin states, but how chromatin features can be inherited through DNA replication is incompletely understood. We address this question using cell-free replication of chromatin. Previously, we showed that a Polycomb group complex, PRC1, remains continuously associated with chromatin through DNA replication. Here we investigate the mechanism of persistence. We find that a single PRC1 subunit, Posterior sex combs (PSC), can reconstitute persistence through DNA replication. PSC binds nucleosomes and self-interacts, bridging nucleosomes into a stable, oligomeric structure. Within these structures, individual PSC-chromatin contacts are dynamic. Stable association of PSC with chromatin, including through DNA replication, depends on PSC-PSC interactions. Our data suggest that labile individual PSC-chromatin contacts allow passage of the DNA replication machinery while PSC-PSC interactions prevent PSC from dissociating, allowing it to rebind to replicated chromatin. This mechanism may allow inheritance of chromatin proteins including PRC1 through DNA replication to maintain chromatin states.
表观遗传调控可能涉及可遗传的染色质状态,但染色质特征如何通过 DNA 复制遗传尚不完全清楚。我们使用无细胞染色质复制来解决这个问题。以前,我们表明多梳复合物 PRC1 通过 DNA 复制持续与染色质结合。在这里,我们研究了持久性的机制。我们发现单个 PRC1 亚基 Posterior sex combs (PSC) 可以通过 DNA 复制重新构建持久性。PSC 结合核小体并自我相互作用,将核小体桥接成稳定的寡聚结构。在这些结构中,单个 PSC-染色质接触是动态的。PSC 与染色质的稳定结合,包括通过 DNA 复制,取决于 PSC-PSC 相互作用。我们的数据表明,不稳定的单个 PSC-染色质接触允许 DNA 复制机制通过,而 PSC-PSC 相互作用阻止 PSC 解离,从而允许其重新结合复制的染色质。这种机制可能允许包括 PRC1 在内的染色质蛋白通过 DNA 复制遗传,以维持染色质状态。