TRANSCRIPTION OF THE E2F-1 GENE IS RENDERED CELL-CYCLE DEPENDENT BY E2F DNA-BINDING SITES WITHIN ITS PROMOTER
TRANSCRIPTION OF THE E2F-1 GENE IS RENDERED CELL-CYCLE DEPENDENT BY E2F DNA-BINDING SITES WITHIN ITS PROMOTER
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DOI：
10.1128/mcb.14.10.6607
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发表时间：
1994-10-01
影响因子：
5.3
通讯作者：
KAELIN, WG
中科院分区：
文献类型：
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作者：
NEUMAN, E;FLEMINGTON, EK;KAELIN, WG
细胞周期调节转录因子E2 F-1通过与蛋白质如视网膜母细胞瘤基因产物的相互作用以及E2 F-1 mRNA丰度的细胞周期依赖性改变来调节。为了更好地理解后一种现象，我们分离了人E2 F-1启动子。与荧光素酶cDNA融合的人E2 F-1启动子在转染到哺乳动物细胞中后产生细胞周期依赖性荧光素酶活性，其方式与先前报道的E2 F-1 mRNA丰度的变化不同。E2 F-1启动子含有四个潜在的E2 F结合位点，组织为两个不完全回文序列。凝胶位移和反式激活研究表明，这些网站可以结合E2 F在体外和体内。两个E2 F回文突变消除了E2 F-1启动子的细胞周期依赖性。因此，E2 F-1似乎在转录水平上受到调节，并且这种调节至少部分是由于一个或多个E2 F家族成员与E2 F-1启动子的结合。
The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fused to a luciferase cDNA, gave rise to cell cycle-dependent luciferase activity upon transfection into mammalian cells in a manner Which paralleled previously reported changes in E2F-1 mRNA abundance. The E2F-1 promoter contains four potential E2F-binding sites organized as two imperfect palindromes. Gel shift and transactivation studies suggested that these sites can bind to E2F in vitro and in vivo. Mutation of the two E2F palindromes abolished the cell cycle dependence of the E2F-1 promoter. Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter.