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当转录因子水平通过核输出而非降解而被急性降低时,靶基因的反应会有所不同。

Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation.

机构信息

California Institute of Technology, Division of Biology and Biological Engineering, 1200 East California Boulevard, Pasadena, CA 91125, USA.

出版信息

Development. 2024 Nov 1;151(21). doi: 10.1242/dev.202775. Epub 2024 Nov 8.

DOI:10.1242/dev.202775
PMID:39397716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11574349/
Abstract

Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.

摘要

定义形态发生素的作用时间需要能够进行时间控制的扰动的工具。为了研究转录因子 Dorsal 如何影响果蝇胚胎背腹轴的模式形成,我们使用了两种光诱导标签,它们可以在蓝光下触发 Dorsal 的核输出或降解。Dorsal 的核输出导致高阈值、腹侧表达的靶基因 snail (sna)丢失,而低阈值、侧向表达的靶基因 short-gastrulation (sog)则被保留。相比之下,Dorsal 的降解导致 sna 的保留、sog 的丢失以及与 Dorsal 从核内输出相比核内水平降低。为了了解为什么核输出导致 sna 的丢失而降解不会,我们使用光漂白研究了 Dorsal 的动力学,发现即使在有利于输出的蓝光条件下,它也能迅速重新进入核内。Dorsal 被快速输入和输出的相关动力学可能是 sna 丢失的原因,但也可以支持 sog。总的来说,我们的结果表明,这种动态模式形成过程受到 Dorsal 浓度和核保留的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/94e1b6a1b519/develop-151-202775-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/957a9c9495bc/develop-151-202775-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/088a74c2be7b/develop-151-202775-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/25bb259b533d/develop-151-202775-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/eb42aa3ea3dc/develop-151-202775-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/75576d0b9eab/develop-151-202775-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/362e827f3e7a/develop-151-202775-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/94e1b6a1b519/develop-151-202775-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/957a9c9495bc/develop-151-202775-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/088a74c2be7b/develop-151-202775-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/25bb259b533d/develop-151-202775-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/eb42aa3ea3dc/develop-151-202775-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/75576d0b9eab/develop-151-202775-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/362e827f3e7a/develop-151-202775-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/304e/11574349/94e1b6a1b519/develop-151-202775-g7.jpg

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