A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1
A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1
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DOI：
10.1194/jlr.m900289-jlr200
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发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
Adamski, J.
中科院分区：
文献类型：
--
作者：
Lattka, E.;Eggers, S.;Adamski, J.
脂肪酸去饱和酶（FADS）在ω-6和ω-3高度不饱和脂肪酸（HUFA）的形成中起重要作用。人代谢组中HUFA的组成对于膜流动性和调节基本生理功能（如炎症过程和脑发育）非常重要。最近的几项研究报道了人类FADS基因簇中的单核苷酸多态性（SNP）与HUFA水平和组成的显着关联。次要等位基因的存在与去饱和酶反应产物的减少和底物的积累相关。我们进行了两个相关的多态性（rs3834458和rs 968567）的功能研究，并通过荧光素酶报告基因测定显示多态性rs 968567对FADS 2启动子活性的影响。电泳迁移率变动分析证明了等位基因依赖的DNA结合能力的至少两个蛋白质复合物的区域含有SNP rs 968567。以等位基因特异性方式与该区域结合的蛋白质之一被证明是转录因子ELK 1（ETS结构域转录因子家族的成员）。这些结果表明，rs 968567影响FADS 2转录，并提供了通过SNP调节FADS 2基因转录的复杂调控机制的第一个见解。Lattka，E.，S. Eggers，G. Moeller，K.海姆，M.韦伯，D。Mehta，H.普罗基施，T。Illig，and J. Adamski.常见的FADS 2启动子多态性增加启动子活性并促进转录因子ELK 1的结合。J. Lipid Res. 2010. 51：182-191。
Fatty acid desaturases (FADS) play an important role in the formation of omega-6 and omega-3 highly unsaturated fatty acids (HUFAs). The composition of HUFAs in the human metabolome is important for membrane fluidity and for the modulation of essential physiological functions such as inflammation processes and brain development. Several recent studies reported significant associations of single nucleotide polymorphisms (SNPs) in the human FADS gene cluster with HUFA levels and composition. The presence of the minor allele correlated with a decrease of desaturase reaction products and an accumulation of substrates. We performed functional studies with two of the associated polymorphisms (rs3834458 and rs968567) and showed an influence of polymorphism rs968567 on FADS2 promoter activity by luciferase reporter gene assays. Electrophoretic mobility shift assays proved allele-dependent DNA-binding ability of at least two protein complexes to the region containing SNP rs968567. One of the proteins binding to this region in an allele-specific manner was shown to be the transcription factor ELK1 (a member of ETS domain transcription factor family). These results indicate that rs968567 influences FADS2 transcription and offer first insights into the modulation of complex regulation mechanisms of FADS2 gene transcription by SNPs.-Lattka, E., S. Eggers, G. Moeller, K. Heim, M. Weber, D. Mehta, H. Prokisch, T. Illig, and J. Adamski. A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J. Lipid Res. 2010. 51: 182-191.