Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication
- PMID: 40779393
- PMCID: PMC12425142
- DOI: 10.1016/j.celrep.2025.116121
Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication
Abstract
Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here, we examine the concentration-dependent regulation of hunchback by the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling, and epigenomics in Drosophila embryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by the hunchback P2 (hbP2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explain in vivo onset time distributions by accounting for both the competition between Bicoid and nucleosomes at hbP2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary of hunchback expression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary of hunchback expression.
Keywords: CP: Developmental biology; CP: Molecular biology; DNA replication; Drosophila; Embryonic patterning; MS2 reporter; chromatin; computational modeling; morphogen; nucleosome; transcription factor.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
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Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication.bioRxiv [Preprint]. 2024 Dec 12:2024.12.10.627802. doi: 10.1101/2024.12.10.627802. bioRxiv. 2024. Update in: Cell Rep. 2025 Aug 26;44(8):116121. doi: 10.1016/j.celrep.2025.116121. PMID: 39713295 Free PMC article. Updated. Preprint.
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