Kawamori Akihito, Shimaji Kouhei, Yamaguchi Masamitsu
Department of Applied Biology and Insect Biomedical Research Center, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan.
Genesis. 2013 Nov;51(11):741-50. doi: 10.1002/dvg.22419. Epub 2013 Aug 30.
DREF (DNA replication-related element-binding factor), a zinc finger type transcription factor required for proper cell cycle progression in both mitotic and endocycling cells, is a positive regulator of E2F1, an important transcription factor which regulates genes related to the S-phase of the cell cycle. DREF and E2F1 regulate similar sets of replication-related genes, including proliferating cell nuclear antigen (PCNA), and play roles in the G1 to S phase transition. However, the relationships between dref and e2f1 or PCNA during development are poorly understood. Here, we provided evidence for novel control of e2f1 and PCNA involving DREF in endocycling cells. Somatic clone analysis demonstrated that dref knockdown stabilized E2F1 expression at posttranscriptional levels in endocycling salivary gland cells. Similarly, PCNA expression was up-regulated in the endocycling salivary gland cells. Genetic interaction analysis indicated that the endoreplication defects are partly caused via possible enhancement of E2F1 activity. From these results and previous reports, we conclude that regulation of e2f1 and PCNA by DREF in vivo is complex and the regulation mechanism may differ with the tissue and/or positions in the tissue.
DREF(DNA复制相关元件结合因子)是一种锌指型转录因子,在有丝分裂细胞和内循环细胞中正常的细胞周期进程中是必需的,它是E2F1的正调控因子,E2F1是一种重要的转录因子,可调节与细胞周期S期相关的基因。DREF和E2F1调节相似的一组与复制相关的基因,包括增殖细胞核抗原(PCNA),并在G1期到S期的转变中发挥作用。然而,在发育过程中dref与e2f1或PCNA之间的关系尚不清楚。在这里,我们提供了证据,证明在循环细胞中存在涉及DREF的e2f1和PCNA的新型调控。体细胞克隆分析表明,dref敲低在转录后水平稳定了循环唾液腺细胞中E2F1的表达。同样,PCNA表达在循环唾液腺细胞中上调。遗传相互作用分析表明,内复制缺陷部分是由于E2F1活性可能增强所致。根据这些结果和以前的报道,我们得出结论,DREF在体内对e2f1和PCNA的调控是复杂的,调控机制可能因组织和/或组织中的位置而异。