Wang Xian-Feng, Liu Jin-Xiao, Ma Zhi-Yuan, Shen Yang, Zhang Hao-Ran, Zhou Zi-Zhang, Suzuki Emiko, Liu Qing-Xin, Hirose Susumu
Department of Gene Function and Phenomics, National Institute of Genetics, 1111 Yata, Mishima City, Shizuoka 411-8540, Japan; State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong 271018, China.
State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong 271018, China.
iScience. 2020 Aug 21;23(8):101369. doi: 10.1016/j.isci.2020.101369. Epub 2020 Jul 15.
Cyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to induce cyclin E in Drosophila. Functional binding motifs of Apt and E2f1 are clustered in the first intron of Drosophila cyclin E and directly contribute to the cyclin E transcription. Knockout of apt and e2f1 together abolished Cyclin E expression. Furthermore, Apt up-regulates Retinoblastoma family protein 1 (Rbf1) for proper chromatin compaction, which is known to repress cyclin E. Notably, Apt-dependent up-regulation of Cyclin E and Rbf1 is evolutionarily conserved in mammalian cells. Our findings reveal a unique mechanism underlying the induction and subsequent decline of Cyclin E expression.
细胞周期蛋白E是进入S期的关键因子，细胞周期蛋白E的失调会导致发育缺陷和肿瘤。因此，细胞周期蛋白E的正常循环对于正常生长至关重要。我们发现转录因子Apontic（Apt）和E2f1在果蝇中协同诱导细胞周期蛋白E。Apt和E2f1的功能性结合基序聚集在果蝇细胞周期蛋白E的第一个内含子中，并直接促进细胞周期蛋白E的转录。同时敲除apt和e2f1会消除细胞周期蛋白E的表达。此外，Apt上调视网膜母细胞瘤家族蛋白1（Rbf1）以实现适当的染色质压实，已知Rbf1可抑制细胞周期蛋白E。值得注意的是，Apt依赖的细胞周期蛋白E和Rbf1上调在哺乳动物细胞中具有进化保守性。我们的研究结果揭示了细胞周期蛋白E表达诱导及随后下降的独特机制。
