A NuRD Complex from Xenopus laevis Eggs Is Essential for DNA Replication during Early Embryogenesis.
A NuRD Complex from Xenopus laevis Eggs Is Essential for DNA Replication during Early Embryogenesis.
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DOI：
10.1016/j.celrep.2018.02.015
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Krude T
中科院分区：
文献类型：
--
作者：
Christov CP;Dingwell KS;Skehel M;Wilkes HS;Sale JE;Smith JC;Krude T
非洲爪蟾胚胎的DNA复制在囊胚中期转变（MBT）发生了显著的变化，在特定的起始点由Y RNA非依赖性的随机起始转变为Y RNA依赖性的起始。在这里，我们确定xNuRD，一个MTA 2的核小体重塑和组蛋白脱乙酰化复合物NuRD的组合，作为一个必不可少的因素在前MBT非洲爪蟾胚胎，克服了在DNA复制过程中Y RNA的功能要求。人NuRD复合物具有与xNuRD不同的亚基组成，并且不支持DNA复制的Y RNA非依赖性起始。xNuRD的阻断或免疫耗竭抑制体外分离细胞核中的DNA复制起始，并导致早期胚胎中的DNA合成抑制、发育延迟和胚胎致死。xNuRD活性在MBT后下降，与复合物的解离和Y RNA依赖性起始的出现一致。因此，我们的数据揭示了一个NuRD复杂的DNA复制因子在早期非洲爪蟾发育过程中的重要作用。xNuRD是DNA复制和非洲爪蟾发育所必需的，在MBT xNuRD可以功能性地取代非编码Y RNA以启动DNA复制之前，xNuRD复合物由CHD 4、MTA 2、HDACm、MBD 3、GATAD 2和RBBP 4/7亚基组成。显示染色质重塑复合物xNuRD是非洲爪蟾卵和早期胚胎中的重要DNA复制因子。他们证明，xNuRD可以在不存在非编码Y RNA的情况下启动DNA复制，而非编码Y RNA仅在发育后期对复制至关重要。
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. xNuRD is essential for DNA replication and Xenopus development before the MBT xNuRD can functionally substitute for non-coding Y RNAs to initiate DNA replication xNuRD complex consists of CHD4, MTA2, HDACm, MBD3, GATAD2, and RBBP4/7 subunits Human NuRD complexes cannot support Y RNA-independent DNA replication Christov et al. show that the chromatin remodeling complex xNuRD is an essential DNA replication factor in the eggs and early embryos of Xenopus laevis. They demonstrate that xNuRD can initiate DNA replication in the absence of non-coding Y RNAs, which only become essential for replication later in development.
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1080/15384101.2015.1042634
发表时间：
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期刊：
Cell cycle (Georgetown, Tex.)
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