Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
The Francis Crick Institute, Developmental Biology Laboratory, 1 Midland Road, London, NW1 1AT, UK.
Cell Rep. 2018 Feb 27;22(9):2265-2278. doi: 10.1016/j.celrep.2018.02.015.
DNA replication in the embryo of Xenopus laevis changes dramatically at the mid-blastula transition (MBT), with Y RNA-independent random initiation switching to Y RNA-dependent initiation at specific origins. Here, we identify xNuRD, an MTA2-containing assemblage of the nucleosome remodeling and histone deacetylation complex NuRD, as an essential factor in pre-MBT Xenopus embryos that overcomes a functional requirement for Y RNAs during DNA replication. Human NuRD complexes have a different subunit composition than xNuRD and do not support Y RNA-independent initiation of DNA replication. Blocking or immunodepletion of xNuRD inhibits DNA replication initiation in isolated nuclei in vitro and causes inhibition of DNA synthesis, developmental delay, and embryonic lethality in early embryos. xNuRD activity declines after the MBT, coinciding with dissociation of the complex and emergence of Y RNA-dependent initiation. Our data thus reveal an essential role for a NuRD complex as a DNA replication factor during early Xenopus development.
非洲爪蟾胚胎中的 DNA 复制在中囊胚转换（MBT）时发生显著变化，Y RNA 非依赖性随机起始转变为特定起始点的 Y RNA 依赖性起始。在这里，我们鉴定出 xNuRD，一种包含 MTA2 的核小体重塑和组蛋白去乙酰化酶复合物 NuRD 的组装体，是 MBT 前非洲爪蟾胚胎中的必需因子，它克服了 DNA 复制过程中 Y RNA 的功能需求。人 NuRD 复合物的亚基组成与 xNuRD 不同，不支持 DNA 复制的 Y RNA 非依赖性起始。在体外分离的核中阻断或免疫耗竭 xNuRD 会抑制 DNA 复制起始，并导致早期胚胎中 DNA 合成抑制、发育延迟和胚胎致死。xNuRD 的活性在 MBT 后下降，与复合物的解离和 Y RNA 依赖性起始的出现同时发生。因此，我们的数据揭示了 NuRD 复合物作为早期非洲爪蟾发育过程中 DNA 复制因子的重要作用。
