Degen Eleanor A, Croslyn Corinne, Mangan Niall M, Blythe Shelby A
Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston Illinois 60208, USA.
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
bioRxiv. 2024 Dec 12:2024.12.10.627802. doi: 10.1101/2024.12.10.627802.
Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation of by the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics in embryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by the P2 ( P2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explain onset time distributions by accounting for both the competition between Bicoid and nucleosomes at P2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary of expression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary of expression.
转录因子（TFs）尽管受到染色质结构和细胞周期的限制，但仍能调节基因表达。在这里，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，在果蝇胚胎中研究了形态发生素Bicoid对[具体基因名称未给出]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[具体基因名称未给出]P2（[具体基因名称未给出]P2）增强子驱动的转录激活时间直接反映了Bicoid的浓度。我们构建了一个随机模型，该模型通过考虑Bicoid与[具体基因名称未给出]P2处核小体之间的竞争以及DNA复制对转录延伸的负面影响，来解释[具体基因名称未给出]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[具体基因名称未给出]表达的后边界。我们得出结论，TF-核小体竞争是形态发生素Bicoid梯度确定[具体基因名称未给出]表达后边界的分子机制。
