Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter
Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter
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DOI：
10.1038/sj.onc.1206840
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发表时间：
2003-10-23
期刊：
影响因子：
8
通讯作者：
Ikeda, MA
中科院分区：
文献类型：
--
作者：
Araki, K;Nakajima, Y;Ikeda, MA
E2F 转录因子的活性在哺乳动物细胞周期进程中起着至关重要的作用，并通过与口袋蛋白（pRb 及其相关的 p107 和 p130）的物理关联来控制。 E2F1 启动子包含两个重叠的 E2F 结合位点，在 G1/S 转变时以 E2F 依赖性方式被激活。突变实验表明，E2F1 启动子上的远端 E2F 结合位点是 G0 期转录抑制所必需的，而近端 E2F 结合位点则有助于 G1/S 边界的转录激活。与这些结果一致，染色质免疫沉淀测定表明，E2F4/p130 阻遏物复合物特异性结合远端 E2F 结合位点，而 E2F1 和 E2F3 激活剂优先结合近端 E2F 结合位点。测定还表明，E2F4/p130 复合物与远端位点的特异性结合因引入连续抑制位点（细胞周期基因同源区；CHR）的突变而受到显着损害。总而言之，这些发现表明，两个 E2F 结合位点通过与不同组的 E2F 成员相互作用并与邻近的阻遏元件配合，在 E2F1 转录调节中发挥不同的作用。
The activity of E2F transcription factors plays a crucial role in mammalian cell-cycle progression and is controlled by physical association with the pocket proteins (pRb and its related p107 and p130). The E2F1 promoter, which contains two overlapping E2F-binding sites, is activated at the G1/S transition in an E2F-dependent manner. Mutational experiments have shown that the distal E2F-binding site on the E2F1 promoter is required for transcriptional repression in the G0 phase, whereas the proximal E2F-binding site contributes to transcriptional activation at the G1/S boundary. Consistent with these results, chromatin immunoprecipitation assays have revealed that the E2F4/p130 repressor complex specifically binds to the distal E2F-binding site, whereas E2F1 and E2F3 activators preferentially bind to the proximal E2F-binding site. The assays also showed that the specific binding of E2F4/p130 complex to the distal site was dramatically impaired by a mutation introduced into the contiguous repression site ( cell Cycle gene Homology Region; CHR). Taken together, these findings indicate that the two E2F-binding sites play distinct roles in the regulation of E2F1 transcription by interacting with different sets of E2F members and cooperating with the contiguous repressor element.