Two E2F sites control growth-regulated and cell cycle-regulated transcription of the Htf9-a/RanBP1 gene through functionally distinct mechanisms
Two E2F sites control growth-regulated and cell cycle-regulated transcription of the Htf9-a/RanBP1 gene through functionally distinct mechanisms
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DOI：
10.1074/jbc.274.15.10339
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发表时间：
1999-04-09
影响因子：
4.8
通讯作者：
Lavia, P
中科院分区：
文献类型：
--
作者：
Di Fiore, B;Guarguaglini, G;Lavia, P
编码Ran结合蛋白1（RanBP 1）的基因以细胞周期依赖性方式转录。RanBP 1启动子含有两个E2 F因子的结合位点，命名为E2 F-c，位于转录起始点附近，和E2 F-b，位于更远的启动子区域。我们已经发现，远端E2 F-b位点，连同相邻的Spl元件，积极控制在S期转录上调。近端E2 F-C位点在细胞周期中没有明显的作用，但在生长停滞时转录抑制是必需的。蛋白质结合研究表明，每个E2 F网站介导的具体相互作用与个别E2 F家族成员。此外，用诱变的启动子构建体进行的瞬时表达测定表明，每个位点的功能作用还取决于其相对于启动子背景中的其他调控元件的位置。因此，这两个E2 F位点发挥相反的遗传功能，并通过不同的分子机制控制RanBP 1的转录。
The gene encoding Ran-binding protein 1 (RanBP1) is transcribed in a cell cycle-dependent manner. The RanBP1 promoter contains two binding sites for E2F factors, named E2F-c, located proximal to the transcription start, and E2F-b, falling in a more distal promoter region, We have now induced site-directed mutagenesis in both sites. We have found that the distal E2F-b site, together with a neighboring Spl element, actively controls up-regulation of transcription in S phase. The proximal E2F-c site plays no apparent role in cycling cells yet is required for transcriptional repression upon growth arrest. Protein binding studies suggest that each E2F site mediates specific interactions with individual E2F family members. In addition, transient expression assays with mutagenized promoter constructs indicate that the functional role of each site is also dependent on its position relative to other regulatory elements in the promoter context. Thus, the two E2F sites play opposite genetic functions and control RanBP1 transcription through distinct molecular mechanisms.