NF-Y involvement in the polyunsaturated fat inhibition of fatty acid synthase gene transcription.
NF-Y involvement in the polyunsaturated fat inhibition of fatty acid synthase gene transcription.
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DOI：
10.1006/bbrc.2002.6341
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发表时间：
2002-02
影响因子：
3.1
通讯作者：
M. Téran-García;C. Rufo;Manabu T. Nakamura;T. Osborne;S. Clarke
中科院分区：
文献类型：
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作者：
M. Téran-García;C. Rufo;Manabu T. Nakamura;T. Osborne;S. Clarke
膳食多不饱和脂肪（PUFA）使SREBP-1的肝脏含量降低65- 75%，这与脂肪酸合成酶（FAS）基因表达的相当降低有关。SREBP-1的核含量与FAS转录之间的密切关系导致PUFA通过抑制SREBP-1的表达来抑制脂肪生成基因的转录，但该结论是基于相关数据的。事实上，当FAS的胰岛素反应元件的SREBP-1/USF位点突变时，FAS启动子活性的PUFA抑制仅丧失25%。另一方面，突变-99/-93 NF-Y位点使总体启动子活性降低85%，并且消除了50%的FAS启动子活性的PUFA抑制。此外，延伸克隆和转染报告基因分析显示FAS基因在远端区域-7382/-6970含有第二个PUFA反应区（PUFA-RR）。有趣的是，远端PUFA-RR（FAS）与l-丙酮酸激酶基因的PUFA-RR具有许多相似性，而近端PUFA-RR（FAS）与S14和硬脂酰-CoA去饱和酶基因的PUFA-RR相当。
Dietary polyunsaturated fats (PUFA) reduce the hepatic content of SREBP-1 65-75%, and this is paralleled by a comparable decrease in the expression of fatty acid synthase (FAS) gene. The close association between the nuclear content of SREBP-1 and FAS transcription has led to the conclusion that PUFA inhibit lipogenic gene transcription by suppressing SREBP-1 expression, but this conclusion is based upon correlative data. When in fact the SREBP-1/USF sites of the insulin response element of FAS were mutated, only 25% of the PUFA inhibition of FAS promoter activity was lost. On the other hand, mutating the -99/-93 NF-Y site reduced overall promoter activity 85%, and eliminated 50% of the PUFA suppression of FAS promoter activity. In addition, extended cloning and transfection-reporter assays revealed that the FAS gene contains a second PUFA response region (PUFA-RR) in the distal area of -7382/-6970. Interestingly, the distal PUFA-RR(FAS) has many similarities to the PUFA-RR of l-pyruvate kinase gene while the proximal PUFA-RR(FAS) is comparable to the PUFA-RR of the S14 and stearoyl-CoA desaturase genes.