Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners
Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners
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DOI：
10.1038/sj.onc.1209210
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发表时间：
2006-03-01
期刊：
影响因子：
8
通讯作者：
Ohtani, K
中科院分区：
文献类型：
--
作者：
Iwanaga, R;Komori, H;Ohtani, K
转录因子E2F介导对响应于生长刺激的细胞增殖重要的基因的细胞周期依赖性表达。为了进一步了解E2F的作用，我们利用灵敏的减法来探索新的E2F1靶点，这些靶点在低水平表达，并且可能在以前的研究中未被识别。我们确定了33个新的E2F1诱导基因，包括检查点基因Claspin和Rad51ap1，以及4个细胞周期进程所需的功能未知的基因。此外，我们发现了三组E2F1诱导的基因，不诱导生长刺激。至少有两组基因被E2F1直接诱导，表明E2F1可以调节细胞周期中未被诱导的基因的表达。其中包括再生蛋白，WASF1和SGEF基因，它们可能在分化或发育中发挥作用。另一个是细胞周期蛋白依赖性激酶抑制剂p27（Kip1），它参与抑制由E2F失调诱导的不适当的细胞周期进程。这些基因的E2F1响应区域位于比典型E2F靶基因更上游的位置，并且没有典型的E2F位点。这些结果表明，存在E2F1靶标组，其以与典型E2F靶标不同的方式调节。
The transcription factor E2F mediates cell cycle-dependent expression of genes important for cell proliferation in response to growth stimulation. To further understand the role of E2F, we utilized a sensitive subtraction method to explore new E2F1 targets, which are expressed at low levels and might have been unrecognized in previous studies. We identified 33 new E2F1-inducible genes, including checkpoint genes Claspin and Rad51ap1, and four genes with unknown function required for cell cycle progression. Moreover, we found three groups of E2F1-inducible genes that were not induced by growth stimulation. At least, two groups of genes were directly induced by E2F1, indicating that E2F1 can regulate expression of genes not induced during the cell cycle. One included Neogenin, WASF1 and SGEF genes, which may have a role in differentiation or development. The other was the cyclin-dependent kinase inhibitor p27(Kip1), which was involved in suppression of inappropriate cell cycle progression induced by deregulated E2F. E2F1-responsive regions of these genes were located more upstream than those of typical E2F targets and did not have typical E2F sites. These results indicate that there are groups of E2F1 targets, which are regulated in a distinct manner from that of typical E2F targets.