Cooperative regulation of CYP3A5 gene transcription by NF-Y and Sp family members
Cooperative regulation of CYP3A5 gene transcription by NF-Y and Sp family members
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DOI：
10.1006/bbrc.2001.5352
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发表时间：
2001-08-10
影响因子：
3.1
通讯作者：
Kamataki, T
中科院分区：
文献类型：
--
作者：
Iwano, S;Saito, T;Kamataki, T
本研究的目的是阐明负责人CYP 3A 5基因转录调控的机制。将一系列5 '端截短的启动子-荧光素酶嵌合基因转染人肝癌细胞HepG 2，发现CYP 3A 5基因的-90 ~-40核苷酸区域参与其转录活性。用HepG 2细胞核提取物进行凝胶迁移试验，结果显示核因子Y（NF-Y）和特异性蛋白（Sp）1和Sp 3分别与CYP 3A 5基因的CCAAT盒（-78/-68）和基本转录元件（BTE）（-67/-46）结合。此外，在CCAAT盒、BTE或这两个元件中引入突变将转录活性降低至完整基因所见的10%、21%或4%。因此，我们得出结论，在HepG 2细胞中，CYP 3A 5基因的转录是由NF-Y，Sp1和Sp3协同调节的。(C)北京：科学出版社.
The purpose of this study was to clarify the mechanism(s) responsible for the transcriptional regulation of the human CYP3A5 gene. It was found that a region from nucleotides -90 to -40 was involved in the transcriptional activity of the CYP3A5 gene by transfection of a series of 5 ' -truncated promoter-luciferase chimeric genes into human hepatoma HepG2 cells. A gel shift assay using nuclear extracts prepared from HepG2 cells showed that nuclear factor-Y (NF-Y) and specificity protein (Sp) 1 and Sp3 bound to CCAAT box (-78/-68) and a basic transcription element (BTE) (-67/-46) in the CYP3A5 gene. Furthermore, introduction of mutations in the CCAAT box, the BTE, or both elements decreased the transcriptional activity to 10, 21, or 4% of that seen with the intact gene. Thus, we conclude that the transcription of the CYP3A5 gene is cooperatively regulated by NF-Y, Sp1, and Sp3 in HepG2 cells. (C) 2001 Academic Press.