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The molecular mechanism regulating the autonomous circadian expression of Topoisomerase I in NIH3T3 cells |
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| Authors: | Fang Yang Yoshihiro Nakajima Yoshihiro Ohmiya |
| Affiliation: | a Department of Physiology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan b Molecular Clock Project, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, 1397-1Yamane, Hidaka, Saitama 350-1241, Japan c Cell Dynamics Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan |
| Abstract: | To identify whether Topoisomerase I (TopoI) has autonomous circadian rhythms regulated by clock genes, we tested mouse TopoI (mTopoI) promoter oscillation in NIH3T3 cells using a real-time monitoring assay and TopoI mRNA oscillations using real-time RT-PCR. Analysis of the mTopoI promoter region with Matlnspector software revealed two putative E-box (E1 and E2) and one DBP/E4BP4-binding element (D-box). Luciferase assays indicated that mTopoI gene expression was directly regulated by clock genes. The real-time monitoring assay showed that E-box and D-box response elements participate in the regulation of the circadian expression of mTopoI. Furthermore, a gel-shift assay showed that E2 is a direct target of the BMAL1/CLOCK heterodimer and DBP binds to the putative D-site. These results indicate that TopoI is expressed in an autonomous circadian rhythm in NIH3T3 cells. |
| Keywords: | Topoisomerase I Circadian rhythms Promoter analysis Antitumor drugs Clock genes |
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