Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis

Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis
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DOI:
10.1073/pnas.1404657111
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发表时间:
2014-07-15
影响因子:
11.1
通讯作者:
Coruzzi, Gloria M.
Coruzzi, Gloria M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Para, Alessia;Li, Ying;Coruzzi, Gloria M.

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基因调控网络的动态特性使细胞能够迅速对环境变化作出反应。然而,即使在动力学研究中,潜在的时间连接也被遗漏了,因为转录因子(TF)在至少一个时间点内结合才能确定主要靶点。受tf调节但未结合的基因被视为次要目标。相反,我们报告这些基因包含与快速信号转导最相关的瞬时tf靶相互作用。我们暂时干扰了一个主TF (Basic Leucine Zipper 1, bZIP1)和它转导的氮(N)信号,并整合了来自同一细胞样本的TF调节和结合数据。我们的方法可以在没有TF结合的情况下,仅基于基因调控来识别主要的TF靶点。我们发现了三类主要的TF靶点:(i)平衡(TF结合但不受TF调节),(ii)稳定(TF结合和受TF调节),以及(iii)瞬时(TF调节但不受TF结合),这是最大的一类。出乎意料的是,瞬时bZIP1靶点与植物的快速N信号传导有关,富含动态N响应基因,并受TF和N信号相互作用的调节。这些瞬时靶标包括早期N应答者硝酸盐转运蛋白2.1和N-样蛋白3,它们在1-5分钟内与bZIP1结合,但在TF扰动后的较晚时间点不与bZIP1结合。此外,这些瞬时靶点的启动子独特地富含与bZIP1结合位点共遗传的顺式调控基序,这表明bZIP1具有招募作用。这种TF作用的瞬时模式支持一种经典的,但被遗忘的“打了就跑”的转录模型,该模型使“催化剂TF”能够在信号扰动的几分钟内激活大量目标。
The dynamic nature of gene regulatory networks allows cells to rapidly respond to environmental change. However, the underlying temporal connections are missed, even in kinetic studies, as transcription factor (TF) binding within at least one time point is required to identify primary targets. The TF-regulated but un-bound genes are dismissed as secondary targets. Instead, we report that these genes comprise transient TF-target interactions most relevant to rapid signal transduction. We temporally perturbed a master TF (Basic Leucine Zipper 1, bZIP1) and the nitrogen (N) signal it transduces and integrated TF regulation and binding data from the same cell samples. Our enabling approach could identify primary TF targets based solely on gene regulation, in the absence of TF binding. We uncovered three classes of primary TF targets: (i) poised (TF-bound but not TF-regulated), (ii) stable (TF-bound and TF-regulated), and (iii) transient (TF-regulated but not TF-bound), the largest class. Unexpectedly, the transient bZIP1 targets are uniquely relevant to rapid N signaling in planta, enriched in dynamic N-responsive genes, and regulated by TF and N signal interactions. These transient targets include early N responders nitrate transporter 2.1 and NIN-like protein 3, bound by bZIP1 at 1-5 min, but not at later time points following TF perturbation. Moreover, promoters of these transient targets are uniquely enriched with cis-regulatory motifs coinherited with bZIP1 binding sites, suggesting a recruitment role for bZIP1. This transient mode of TF action supports a classic, but forgotten, "hit-and-run" transcription model, which enables a "catalyst TF" to activate a large set of targets within minutes of signal perturbation.