A NuRD Complex from Xenopus laevis Eggs Is Essential for DNA Replication during Early Embryogenesis

Abstract

Summary: 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. : 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. Keywords: DNA replication, initiation, Xenopus laevis, mid-blastula transition, development, NuRD, chromatin remodeling, histone deacetylase, non-coding RNA, Y RNA