A model Notch response element detects Suppressor of Hairless-dependent molecular switch
A model Notch response element detects Suppressor of Hairless-dependent molecular switch
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DOI：
10.1016/s0960-9822(00)00044-0
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发表时间：
2001-01-09
期刊：
影响因子：
9.2
通讯作者：
Bray, S
中科院分区：
文献类型：
--
作者：
Furriols, M;Bray, S
Notch介导的细胞-细胞信号传导在许多不同的发育过程中对于细胞命运的规范或限制至关重要。目前，唯一已知的转导途径涉及DNA结合蛋白，果蝇中的无毛抑制因子[Su（H）]和哺乳动物中的CBF 1，并导致靶基因的直接激活。有人提出，在没有Notch的情况下，Su（H）/CBF 1作为阻遏物，并通过与Notch细胞内结构域的相互作用转化为激活物[1-4]。最近，我们还提出，特定靶基因的激活需要Su（H）和其他转录激活物之间的协同作用[5]。我们的结果清楚地表明，Su（H）能够作为分子开关的核心发挥作用，在Notch不存在的情况下抑制转录，在Notch存在的情况下激活。在其作为激活剂的能力中，Su（H）可以与RNA结合的转录因子Grainyhead协同合作。这些相互作用表明Notch靶基因调控的简单模型，其可以解释Notch信号传导在不同发育命运决定中引起的基因激活的精确性。
Cell-cell signaling mediated by Notch is critical during many different developmental processes for the specification or restriction of cell fates. Currently, the only known transduction pathway involves a DNA binding protein, Suppressor of Hairless [Su(H)] in Drosophila and CBF1 in mammals, and results in the direct activation of target genes. It has been proposed that in the absence of Notch, Su(H)/CBF1 acts as a repressor and is converted into an activator through interactions with the Notch intracellular domain [1-4], Recently, we have also suggested that the activation of specific target genes requires synergy between Su(H) and other transcriptional activators [5] Here we have designed an assay that allows us to directly test these hypotheses in vivo. Our results clearly demonstrate that Su(H) is able to function as the core of a molecular switch, repressing transcription in the absence of Notch and activating in the presence of Notch. In its capacity as an activator, Su(H) can cooperate synergistically with a RNA-bound transcription factor, Grainyhead, These interactions indicate a simple model for Notch target-gene regulation that could explain the precision of gene activation elicited by Notch signaling in different developmental fate decisions.