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两种PAR亮氨酸拉链蛋白，即TEF和DBP，表现出相似的昼夜节律和组织特异性表达，但具有不同的靶启动子偏好。

The two PAR leucine zipper proteins, TEF and DBP, display similar circadian and tissue-specific expression, but have different target promoter preferences.

作者信息

Fonjallaz P, Ossipow V, Wanner G, Schibler U

机构信息

Département de Biologie Moléculaire, Université de Genève, Switzerland.

出版信息

EMBO J. 1996 Jan 15;15(2):351-62.

PMID:8617210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC449950/
Abstract

The two highly related PAR basic region leucine zipper proteins TEF and DBP accumulate according to a robust circadian rhythm in liver and kidney. In liver nuclei, the amplitude of daily oscillation has been estimated to be 50-fold and 160-fold for TEF and DBP, respectively. While DBP mRNA expression is the principal determinant of circadian DBP accumulation, the amplitude of TEF mRNA cycling is insufficient to explain circadian TEF fluctuation. Conceivably, daily variations in TEF degradation or nuclear translocation efficiency may explain the discrepancy between mRNA and protein accumulation. In vitro, TEF and DBP bind the same DNA sequences. Yet, in co-transfection experiments, these two proteins exhibit different activation potentials for two reporter genes examined. While TEF stimulates transcription from the albumin promoter more potently than DBP, only DBP is capable of activating transcription efficiently from the cholesterol 7 alpha hydroxylase (C7alphaH) promoter. However, a TEF-DBP fusion protein, carrying N-terminal TEF sequences and the DNA binding/dimerization domain of DBP, enhances expression of the C7alphaH-CAT reporter gene as strongly as wild-type DBP. Our results suggest that the promoter environment, rather than the affinity with which PAR proteins recognize their cognate DNA sequences in vitro, determines the promoter preferences of TEF and DBP.

摘要

两种高度相关的PAR碱性区域亮氨酸拉链蛋白TEF和DBP在肝脏和肾脏中按照强劲的昼夜节律进行积累。在肝细胞核中，TEF和DBP每日振荡的幅度估计分别为50倍和160倍。虽然DBP mRNA表达是昼夜节律性DBP积累的主要决定因素，但TEF mRNA循环的幅度不足以解释昼夜节律性TEF的波动。可以想象，TEF降解或核转运效率的每日变化可能解释了mRNA和蛋白质积累之间的差异。在体外，TEF和DBP结合相同的DNA序列。然而，在共转染实验中，这两种蛋白质对所检测的两个报告基因表现出不同的激活潜力。虽然TEF比DBP更有效地刺激白蛋白启动子的转录，但只有DBP能够有效地激活胆固醇7α羟化酶（C7alphaH）启动子的转录。然而，一种携带N端TEF序列和DBP的DNA结合/二聚化结构域的TEF-DBP融合蛋白，与野生型DBP一样强烈地增强C7alphaH-CAT报告基因的表达。我们的结果表明，启动子环境而非PAR蛋白在体外识别其同源DNA序列的亲和力，决定了TEF和DBP对启动子的偏好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/8edd52ae219f/emboj00002-0161-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7d0fdeb3b3a6/emboj00002-0154-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7340650eb944/emboj00002-0155-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7f274dc8505d/emboj00002-0156-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/58d75d56bf2d/emboj00002-0157-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/691e3b3b3545/emboj00002-0158-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/07bc5f4d2db2/emboj00002-0160-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/8edd52ae219f/emboj00002-0161-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7d0fdeb3b3a6/emboj00002-0154-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7340650eb944/emboj00002-0155-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/7f274dc8505d/emboj00002-0156-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/58d75d56bf2d/emboj00002-0157-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/691e3b3b3545/emboj00002-0158-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/07bc5f4d2db2/emboj00002-0160-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f96/449950/8edd52ae219f/emboj00002-0161-a.jpg

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