Epigenetics & Neurobiology Unit, European Molecular Biology Laboratory (EMBL Rome), Monterotondo, Italy.
Institute of Cell Biology, School of Biological Sciences University of Edinburgh, Edinburgh, UK.
Nat Commun. 2021 May 18;12(1):2910. doi: 10.1038/s41467-021-22899-2.
Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture.
三维基因组组织和复制时间已知是相关的，然而，核结构是否总体上对复制时间程序起着指导作用，以及如果是这样，其作用方式如何，目前尚不清楚。在这里，我们证明 RIF1 是一个分子枢纽，共同调节这两个过程。核结构和复制时间都依赖于 RIF1 和 PP1 之间的相互作用。然而，尽管核结构需要完整的 RIF1 及其与 PP1 的相互作用，但复制时间对 RIF1 剂量不敏感。RIF1 在复制时间中的作用也超出了其与 PP1 的相互作用。利用这种功能分离的方法，我们因此确定了 RIF1 的双重功能，即复制时间程序和核结构的相互依存关系的分子基础。
