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This content will become publicly available on December 12, 2025

Title: Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication
SUMMARY Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation ofhunchbackby the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics inDrosophilaembryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by thehunchbackP2 (hbP2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explainin vivoonset time distributions by accounting for both the competition between Bicoid and nucleosomes athbP2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary ofhunchbackexpression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary ofhunchbackexpression.  more » « less
Award ID(s):
2235451
PAR ID:
10611993
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
bioRxiv
Date Published:
Format(s):
Medium: X
Institution:
bioRxiv
Sponsoring Org:
National Science Foundation
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