Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program

作者：Foti Rossana; Gnan Stefano; Cornacchia Daniela; Dileep Vishnu; Bulut Karslioglu Aydan; Diehl Sarah; Buness Andreas; Klein Felix A; Huber Wolfgang; Johnstone Ewan; Loos Remco; Bertone Paul; Gilbert David M; Manke Thomas; Jenuwein Thomas; Buonomo Sara C B^*

来源：Molecular Cell, 2016, 61(2): 260-273.

DOI：10.1016/j.molcel.2015.12.001

DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control and biological function of the replication-timing program are unclear. Rif1 is required for normal genome-wide regulation of replication timing, but its molecular function is poorly understood. Here we show that in mouse embryonic stem cells, Rif1 coats late-replicating domains and, with Lamin B1, identifies most of the late-replicating genome. Rif1 is an essential determinant of replication timing of non-Lamin B1-bound late domains. We further demonstrate that Rif1 defines and restricts the interactions between replication-timing domains during the G1 phase, thereby revealing a function of Rif1 as organizer of nuclear architecture. Rif1 loss affects both number and replication-timing specificity of the interactions between replication-timing domains. In addition, during the S phase, Rif1 ensures that replication of interacting domains is temporally coordinated. In summary, our study identifies Rif1 as the molecular link between nuclear architecture and replication-timing establishment in mammals.

• 出版日期2016-1-21