Notch/Hairless 通路在胃形成前奏中对 sog 转录突变的调控

Kelli D. Fenelon, Priyanshi Borad, Biraaj Rout, Parisa Boodaghimalidarreh, Mohammad S. Nasr, Jacob Luber, Theodora Koromila
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摘要

转录调节是由转录因子(TF)和增强子之间的相互作用协调的,它控制着对细胞过程至关重要的基因表达动态。虽然转录因子依赖性基因表达模式的粗略定性波动已有很长的表征历史,但现在利用现代技术可以观察到这些因子在细胞核中的作用,即在这些因子存在或不存在的情况下保持表达。我们的研究以果蝇早期胚胎为模型系统,研究了无毛抑制因子(Su(H))(一种广泛表达的转录因子)对增强子驱动的转录调制的影响。在之前研究结果的基础上,我们利用超分辨率显微镜,在没有 Su(H) 结合的情况下,特异性地在保留了 sogD 驱动表达的细胞核中剖析了 Su(H) 对 sog-Distal(sogD)增强子活性的影响。我们证明,Su(H)占位扰动改变了表达水平和猝发动态。值得注意的是,在胚胎发育过程中,Su(H)的缺失表现出区域特异性效应,在背侧抑制表达,而在腹侧增强表达,这意味着Su(H)在增强子调控中起着微妙的作用。我们的发现揭示了支配转录动态的复杂机制,并表明当胚胎过渡到胃形成时,Notch/Hairless 信号在 sog 表达中起着关键的模式化作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Notch/Hairless Pathway Modulation of sog Transcriptional Bursting in Prelude to Gastrulation
Transcriptional regulation, orchestrated by the interplay between transcription factors (TFs) and enhancers, governs gene expression dynamics crucial for cellular processes. While gross, qualitative fluctuations in transcription factor-dependent gene expression patterning have a long history of characterization, the roles of these factors in the nuclei retaining expression in the presence or absence of these factors are now observable using modern techniques. Our study investigates the impact of Suppressor of Hairless (Su(H)), a broadly expressed transcription factor, on enhancer-driven transcriptional modulation using Drosophila early embryos as a model system. Building upon previous findings, we employ super-resolution microscopy to dissect Su(H)'s influence on sog-Distal (sogD) enhancer activity specifically in nuclei with preserved sogD-driven expression in the absence of Su(H) binding. We demonstrate that Su(H) occupancy perturbations alter expression levels and bursting dynamics. Notably, Su(H) absence during embryonic development exhibits region-specific effects, inhibiting expression dorsally and enhancing expression ventrally, implying a nuanced role in enhancer regulation. Our findings shed light on the intricate mechanisms that govern transcriptional dynamics and suggest a critical patterning role for Notch/Hairless signaling in sog expression as embryos transition to gastrulation.
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