Degen Eleanor A, Croslyn Corinne, Mangan Niall M, Blythe Shelby A
Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
Cell Rep. 2025 Aug 6;44(8):116121. doi: 10.1016/j.celrep.2025.116121.
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.
转录因子（TFs）尽管受到染色质结构和细胞周期的限制，仍能调节基因表达。在此，我们通过定量成像、数学建模和表观基因组学相结合的方法，研究果蝇胚胎中形态发生素双胸（Bicoid）对驼背（hunchback）基因的浓度依赖性调控。通过对MS2报告基因的实时成像，我们发现，有丝分裂后，由驼背P2（hbP2）增强子驱动的转录激活时间直接反映了双胸的浓度。我们构建了一个随机模型，该模型通过考虑双胸与hbP2处核小体之间的竞争以及DNA复制对转录延伸的负面影响，能够解释体内起始时间分布。对核小体稳定性的实验性调节改变了起始时间分布和驼背表达的后边界。我们得出结论，TF-核小体竞争是形态发生素双胸梯度确定驼背表达后边界的分子机制。
