Sequence-specific protein interaction with a transcriptional enhancer involved in the autoregulated expression of cAMP receptor 1 in Dictyostelium.

Sequence-specific protein interaction with a transcriptional enhancer involved in the autoregulated expression of cAMP receptor 1 in Dictyostelium.
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盘基网柄菌中参与 cAMP 受体 1 自动调节表达的转录增强子与序列特异性蛋白质的相互作用。

DOI:
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发表时间:
1998
期刊:
影响因子:
4.6
通讯作者:
Alan R. Kimmel
Alan R. Kimmel
中科院分区:
生物学2区
文献类型:
--
作者:
Xiuqian Mu;Brian Lee;John M. Louis;Alan R. Kimmel

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网骨藻发育的主要阶段由分泌的细胞外cAMP通过激活蛇形受体家族来调节。在早期发育过程中,细胞外cAMP的振荡使细胞聚集;后来,持续暴露于较高的细胞外cAMP浓度下调早期基因表达,并促进细胞分化和细胞特异性基因表达。cAMP受体1基因CAR 1有两个启动子,它们对这些细胞外cAMP刺激有不同的反应。早期CAR 1启动子由cAMP的nM脉冲诱导,cAMP脉冲又由腺苷酸环化酶(AC)的CAR 1依赖性激活产生。更高的,非波动浓度的cAMP将适应这种AC刺激反应,抑制激活的早期启动子并诱导休眠的晚期启动子。我们现在确定了脉冲诱导的CAR 1启动子的关键元件和具有序列特异性相互作用的核因子。元件内四个核苷酸的突变阻止了在体外蛋白结合和在体内表达否则完全活性的早期CAR 1启动子,并且野生型而非突变体序列的多聚化将赋予cAMP调节至静止异源启动子。因此,这些顺式和反式元件构成了对cAMP跨膜信号级联反应的分子应答的一部分,该级联反应调节网骨藻的早期发育。
Major stages of Dictyostelium development are regulated by secreted, extracellular cAMP through activation of a serpentine receptor family. During early development, oscillations of extracellular cAMP mobilize cells for aggregation; later, continuous exposure to higher extracellular cAMP concentrations downregulates early gene expression and promotes cytodifferentiation and cell-specific gene expression. The cAMP receptor 1 gene CAR1 has two promoters that are differentially responsive to these extracellular cAMP stimuli. The early CAR1 promoter is induced by nM pulses of cAMP, which in turn are generated by CAR1-dependent activation of adenylyl cyclase (AC). Higher, non-fluctuating concentrations of cAMP will adapt this AC stimulus-response, repress the activated early promoter and induce the dormant late promoter. We now identify a critical element of the pulse-induced CAR1 promoter and a nuclear factor with sequence-specific interaction. Mutation of four nucleotides within the element prevents both in vitro protein binding and in vivo expression of an otherwise fully active early CAR1 promoter and multimerization of the wild-type, but not mutant, sequence will confer cAMP regulation to a quiescent heterologous promoter. These cis and trans elements, thus, constitute a part of the molecular response to the cAMP transmembrane signal cascade that regulates early development of Dictyostelium.
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