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首页> 外文期刊>Oncogene >Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter
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Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter

机译：E2F家族成员向特定E2F结合位点的不同募集介导E2F1启动子的激活和抑制

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摘要

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.
机译：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，并受与口袋蛋白（pRb及其相关的p107和p130）的物理缔合控制。包含两个重叠的E2F结合位点的E2F1启动子在G1 / S过渡处以E2F依赖的方式被激活。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边界处的转录激活。与这些结果一致，染色质免疫沉淀试验表明，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。该测定还表明，引入到连续抑制位点的突变（细胞周期基因同源区; CHR）显着削弱了E2F4 / p130复合物与远端位点的特异性结合。综上所述，这些发现表明，两个E2F结合位点通过与不同的E2F成员组相互作用并与连续的阻遏物元件协同作用，在E2F1转录的调控中发挥不同的作用。

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