ArticleProceedings of the National Academy of Sciences of the United States of America2015
Histone titration against the genome sets the DNA-to-cytoplasm threshold for the Xenopus midblastula transition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed.
- Differential control of both cell cycle-regulated and quantitative histone mRNA expression bybioRxiv : the preprint server for biology · 2026Article
- SLBP-independent control of maternal histone mRNA.bioRxiv : the preprint server for biology · 2026Article
- Regulation of zygotic genome activation by the nucleocytoplasmic ratio.Frontiers in cell and developmental biology · 2026Review
- Reconstitution of genome remodeling usingFrontiers in cell and developmental biology · 2026Review
- Local nuclear to cytoplasmic ratio regulates H3.3 incorporation via cell cycle state during zygotic genome activation.EMBO reports · 2025Article
- CANTAC-seq analysis reveals E2f1 and Otx1 coordinate zygotic genome activation in Xenopus tropicalis.Nature communications · 2025Article
- Translational repression by 4E-T is crucial to maintain the prophase-I arrest in vertebrate oocytes.Nature communications · 2025Article
- The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus.Nature reviews. Genetics · 2025Review
- Intracellular diffusion in the cytoplasm increases with cell size in fission yeast.Molecular biology of the cell · 2025Article
- Zelda is dispensable forMolecular biology of the cell · 2025Article
- Bellymount-pulsed tracking: a novel approach for real-time in vivo imaging of Drosophila abdominal tissues.G3 (Bethesda, Md.) · 2025Article
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- Canonical and Variant Nucleosome Reprogramming from Sperm to Blastula.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Kick-starting the zygotic genome: licensors, specifiers, and beyond.EMBO reports · 2024Review
- Eukaryotic cell size regulation and its implications for cellular function and dysfunction.Physiological reviews · 2024Review
- Cell cycle length governs heterochromatin reprogramming during early development in non-mammalian vertebrates.EMBO reports · 2024Article
- Quantitative proteomics reveals the dynamic proteome landscape of zebrafish embryos during the maternal-to-zygotic transition.iScience · 2024Article
- Bellymount-Pulsed Tracking: A Novel Approach for Real-Time In vivo Imaging ofbioRxiv : the preprint server for biology · 2024Article
- Collective effects of cell cleavage dynamics.Frontiers in cell and developmental biology · 2024Review
- Coordinated expression of replication-dependent histone genes from multiple loci promotes histone homeostasis inMolecular biology of the cell · 2023Article
42 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
During early development, animal embryos depend on maternally deposited RNA until zygotic genes become transcriptionally active. Before this maternal-to-zygotic transition, many species execute rapid and synchronous cell divisions without growth phases or cell cycle checkpoints. The coordinated onset of transcription, cell cycle lengthening, and cell cycle checkpoints comprise the midblastula transition (MBT). A long-standing model in the frog, Xenopus laevis, posits that MBT timing is controlled by a maternally loaded inhibitory factor that is titrated against the exponentially increasing amount of DNA. To identify MBT regulators, we developed an assay using Xenopus egg extract that recapitulates the activation of transcription only above the DNA-to-cytoplasm ratio found in embryos at the MBT. We used this system to biochemically purify factors responsible for inhibiting transcription below the threshold DNA-to-cytoplasm ratio. This unbiased approach identified histones H3 and H4 as concentration-dependent inhibitory factors. Addition or depletion of H3/H4 from the extract quantitatively shifted the amount of DNA required for transcriptional activation in vitro. Moreover, reduction of H3 protein in embryos induced premature transcriptional activation and cell cycle lengthening, and the addition of H3/H4 shortened post-MBT cell cycles. Our observations support a model for MBT regulation by DNA-based titration and suggest that depletion of free histones regulates the MBT. More broadly, our work shows how a constant concentration DNA binding molecule can effectively measure the amount of cytoplasm per genome to coordinate division, growth, and development.
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