Molecular competition can shape enhancer activity in the Drosophila embryo.
Molecular competition can shape enhancer activity in the Drosophila embryo.
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DOI：
10.1016/j.isci.2021.103034
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发表时间：
2021-09-24
期刊：
影响因子：
5.8
通讯作者：
Wunderlich Z
中科院分区：
文献类型：
--
作者：
Waymack R;Gad M;Wunderlich Z
转基因报告基因可以测量体内 DNA 调控活性，因此长期以来一直是研究增强子的有用工具。尽管它们很实用，但很少有研究调查这些报告基因可能对其他基因表达的影响。需要了解这些影响才能准确解释报告数据并表征基因调控机制。通过测量活果蝇胚胎中 Kruppel (Kr) 增强子报告基因的表达，我们发现报告基因会抑制彼此以及附近内源基因的表达。使用合成转录因子 (TF) 结合位点阵列，我们提供的证据表明，对 TF 的竞争是观察到的转录抑制的部分原因。我们开发了一个简单的热力学模型，可以预测当 TF 结合仅限于不同的核子区域时所测量的竞争程度。我们的研究结果强调了细胞核的非同质性在调节基因表达中的意想不到的作用。转录的实时跟踪揭示了转基因报告基因之间的竞争 转基因报告基因还可以抑制邻近基因的表达 表达抑制部分是由于转录因子 (TF) 的竞争 竞争是通过将 TF 限制在亚核“中心”的模型来预测的 生物科学；分子生物学；分子相互作用；细胞生物学；发育生物学；数学生物科学
Transgenic reporters allow the measurement of regulatory DNA activity in vivo and consequently have long been useful tools for studying enhancers. Despite their utility, few studies have investigated the effects these reporters may have on the expression of other genes. Understanding these effects is required to accurately interpret reporter data and characterize gene regulatory mechanisms. By measuring the expression of Kruppel (Kr) enhancer reporters in live Drosophila embryos, we find reporters inhibit one another’s expression and that of a nearby endogenous gene. Using synthetic transcription factor (TF) binding site arrays, we present evidence that competition for TFs is partially responsible for the observed transcriptional inhibition. We develop a simple thermodynamic model that predicts competition of the measured magnitude specifically when TF binding is restricted to distinct nuclear subregions. Our findings underline an unexpected role of the non-homogenous nature of the nucleus in regulating gene expression. Live tracking of transcription reveals competition between transgenic reporters Transgenic reporters can also depress the expression of a neighboring gene Expression inhibition is in part because of competition for transcription factors (TFs) Competition is predicted with a model that restricts TFs to sub-nuclear “hubs” Biological sciences; Molecular biology; Molecular interaction; Cell biology; Developmental biology; Mathematical biosciences
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DOI：
10.1073/pnas.231608898
发表时间：
2002-01-22
影响因子：
11.1
作者：
Berman, BP;Nibu, Y;Eisen, MB
通讯作者：
Eisen, MB
影响因子：
14.9
作者：
Kazemian M;Pham H;Wolfe SA;Brodsky MH;Sinha S
通讯作者：
Sinha S
影响因子：
3.3
作者：
Chandler, Christopher H.;Chari, Sudarshan;Dworkin, Ian
通讯作者：
Dworkin, Ian
影响因子：
64.5
作者：
Fowlkes, Charless C.;Luengo Hendriks, Cris L.;Malik, Jitendra
通讯作者：
Malik, Jitendra
影响因子：
16.6
作者：
Jung C;Bandilla P;von Reutern M;Schnepf M;Rieder S;Unnerstall U;Gaul U
通讯作者：
Gaul U