Autoregulatory Loop in the Regulation of the Mammalian ftz-f1 Gene (*)
Autoregulatory Loop in the Regulation of the Mammalian ftz-f1 Gene (*)
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哺乳动物 ftz-f1 基因调节中的自动调节环 (*)
DOI：
10.1074/jbc.271.14.8243
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
K. Morohashi
中科院分区：
文献类型：
--
作者：
M. Nomura;H. Nawata;K. Morohashi
哺乳动物FTZ-F1(mftz-F1)基因编码Ad4BP/SF-1，对肾上腺和性腺的发育起重要作用。在先前的研究中，我们确定E盒是大鼠mftz-F1基因5‘-上游区域的转录元件。在本研究中，我们在该基因的第一内含子中发现了一个类固醇生成细胞特异的转录元件。凝胶迁移率漂移和DNase I足迹分析清楚地表明Ad4BP本身与该元件(Ad4位点)结合。Ad4BP表达载体对转录的积极作用以及Ad4位点内核苷酸替换导致的转录显著降低进一步支持了这一发现。E框中的替换也造成了类似的丢失，表明这两个元件对于基因的全部转录活性是必不可少的。DNase I超敏分析显示，肾上腺和Y-1细胞中Ad4位点和E盒周围的染色质结构“开放”，而肝脏则“关闭”。这些观察表明，mftz-F1基因是由类固醇合成组织中的自我调节环控制的。自我调节机制似乎是保持mftz-F1基因激活从而维持组织分化所必需的。
The mammalian ftz-f1 (mftz-f1) gene encoding Ad4BP/SF-1 has been demonstrated to be essential for the development of adrenal and gonadal glands. In a previous study, we identified an E box as the transcriptional element in the 5′-upstream region of the rat mftz-f1 gene. In the present study, we found a steroidogenic cell-specific transcriptional element in the first intron of the gene. Gel mobility shift and DNase I footprint analyses clearly revealed that Ad4BP itself binds to the element (Ad4 site). This finding was further supported by the positive effect of an Ad4BP expression vector on the transcription and by the significant decrease in the transcription caused by nucleotide substitutions within the Ad4 site. Similar loss was also caused by substitutions in the E box, indicating that the two elements are essential for the full transcriptional activity of the gene. DNase I hypersensitivity assays revealed that the chromatin structure around the Ad4 site and the E box was “open up” in the adrenal glands and Y-1 cells, whereas “closed down” in the liver. These observations indicated that the mftz-f1 gene is controlled by the autoregulatory loop in the steroidogenic tissues. The autoregulatory mechanism seems to be necessary to keep the mftz-f1 gene activated and thus maintain the tissues differentiated.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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