Iwanaga R, Komori H, Ishida S, Okamura N, Nakayama K, Nakayama K I, Ohtani K
Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Oncogene. 2006 Mar 16;25(12):1786-98. doi: 10.1038/sj.onc.1209210.
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.
转录因子E2F介导细胞周期依赖性基因表达，这些基因对生长刺激反应中细胞增殖很重要。为进一步了解E2F的作用，我们利用一种灵敏的消减方法来探索新的E2F1靶标，这些靶标表达水平低，可能在以前的研究中未被识别。我们鉴定出33个新的E2F1诱导基因，包括检查点基因Claspin和Rad51ap1，以及细胞周期进程所需的四个功能未知的基因。此外，我们发现三组E2F1诱导基因不受生长刺激诱导。至少两组基因由E2F1直接诱导，表明E2F1可调节细胞周期中未被诱导的基因表达。一组包括Neogenin、WASF1和SGEF基因，它们可能在分化或发育中起作用。另一组是细胞周期蛋白依赖性激酶抑制剂p27（Kip1），它参与抑制由失调的E2F诱导的不适当细胞周期进程。这些基因的E2F1反应区域比典型E2F靶标的更位于上游，且没有典型的E2F位点。这些结果表明存在几组E2F1靶标，它们以与典型E2F靶标不同的方式受到调控。
