Control of DNA Replication by the Nucleus/Cytoplasm Ratio in Xenopus

Murphy, Christopher M.; Michael, W. Matthew

doi:10.1074/jbc.m113.499012

Cited by 25 publications

(20 citation statements)

References 39 publications

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“…A second group also investigated the effect of the nucleus to cytoplasm ratio on the rate of DNA replication in Xenopus egg extracts (Murphy and Michael, 2013). By titrating sperm chromatin, they found that there is an increase in the time required to replicate sperm nuclei at high nucleus to cytoplasm ratios and, consistent with the work of Collart et al (2013), that this is caused by a decrease in replication origin activation.…”

Section: Mechanisms Regulating Changes To the Cell Cyclementioning

confidence: 77%

New insights into the maternal to zygotic transition

Langley¹,

Smith²,

et al. 2014

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The initial phases of embryonic development occur in the absence of de novo transcription and are instead controlled by maternally inherited mRNAs and proteins. During this initial period, cell cycles are synchronous and lack gap phases. Following this period of transcriptional silence, zygotic transcription begins, the maternal influence on development starts to decrease, and dramatic changes to the cell cycle take place. Here, we discuss recent work that is shedding light on the maternal to zygotic transition and the interrelated but distinct mechanisms regulating the onset of zygotic transcription and changes to the cell cycle during early embryonic development.

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Section: Mechanisms Regulating Changes To the Cell Cyclementioning

confidence: 77%

New insights into the maternal to zygotic transition

Langley¹,

Smith²,

et al. 2014

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“…The proposed model is that maternally-derived MBT inhibitors are present in a fixed volume of embryonic cytoplasm, and once a critical genomic DNA amount is reached, titration of these factors by DNA induces the MBT [1, 14]. Recently, a number of potential limiting components have been identified relevant to the Xenopus MBT [34, 37, 38]. Importantly, none of these factors appear to fully account for the abrupt changes in gene expression and cell behavior that occur at the MBT, and it seems likely that redundant mechanisms regulate this critical developmental transition [39, 40].…”

Section: Discussionmentioning

confidence: 99%

“…Early MBT induction by microinjection of plasmid DNA into embryos [14] might also have been mediated through the N/C volume ratio as this injected DNA was subsequently shown to assemble into nuclei [46, 47]. Another possibility is that nuclear volume is relevant to models of MBT timing that invoke titration of an inhibitor by DNA binding, and a notable property of the putative limiting components identified to date is that they all act within the nucleus [34, 37, 38]. Perhaps the MBT is regulated not only by the absolute amounts of key DNA-binding factors that are maternally-derived and titrated by DNA to trigger the MBT, but by their nuclear concentrations, determined by changes in total embryonic nuclear volume during development.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Size Scaling during Xenopus Early Development Contributes to Midblastula Transition Timing

2015

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Summary Early Xenopus laevis embryogenesis is a robust system for investigating mechanisms of developmental timing. After a series of rapid cell divisions with concomitant reductions in cell size, the first major developmental transition is the midblastula transition (MBT), when zygotic transcription begins and cell cycles elongate [1-3]. While the maintenance of a constant nuclear-to-cytoplasmic (N/C) volume ratio is a conserved cellular property [4-7], it has long been recognized that the N/C volume ratio changes dramatically during early Xenopus development [8]. We investigated how changes in nuclear size and the N/C volume ratio during early development contribute to the regulation of MBT timing. While previous studies suggested a role for the N/C volume ratio in MBT timing [1, 9-13], none directly tested the effects of altering nuclear size. In this study, we first quantify blastomere and nuclear sizes in X. laevis embryos, demonstrating that the N/C volume ratio increases prior to the MBT. We then manipulate nuclear volume in embryos by microinjecting different nuclear scaling factors, including import proteins, lamins, and reticulons. Using this approach, we show that increasing the N/C volume ratio in pre-MBT embryos leads to premature activation of zygotic gene transcription and early onset of longer cell cycles. Conversely, decreasing the N/C volume ratio delays zygotic transcription and leads to additional rapid cell divisions. While the DNA-to-cytoplasmic ratio has been implicated in MBT timing [1, 9-18], our data show that nuclear size also contributes to the regulation of MBT timing, demonstrating the functional significance of nuclear size during development.

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“…However, the effects on zygotic transcription were moderate (Collart et al, 2013), consistent with the likely existence of multiple titrated molecules, with some having greater influence on replication and others—such as histones—perhaps having greater influence on transcription (Amodeo et al, 2015; Joseph et al, 2017). In addition to histones and replication factors, other candidate titrated molecules include the phosphatase PP2A-B55 (Murphy and Michael, 2013), maternal histone variants (Yue et al, 2013), the DNA methyl transferase xDnmt1 (Dunican et al, 2008), and dNTPs (Landström et al, 1975; Vastag et al, 2011). …”

Section: Nuclear-to-cytoplasmic Ratio Mechanismsmentioning

confidence: 99%

Zygotic Genome Activation in Vertebrates

2017

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The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription begins. During the MZT, the embryo takes charge of gene expression to control cell differentiation and further development. This spectacular organismal transition requires nuclear reprogramming and the initiation of RNAPII at thousands of promoters. Zygotic genome activation (ZGA) is mechanistically coordinated with other embryonic events including changes in the cell cycle, chromatin state, and nuclear-to-cytoplasmic component ratios. Here, we review progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans to explore differences and emphasize common features.

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Control of DNA Replication by the Nucleus/Cytoplasm Ratio in Xenopus

Cited by 25 publications

References 39 publications

New insights into the maternal to zygotic transition

New insights into the maternal to zygotic transition

Nuclear Size Scaling during Xenopus Early Development Contributes to Midblastula Transition Timing

Zygotic Genome Activation in Vertebrates

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