Exploring the Formation and Recognition of an Important G-Quadruplex in a HIF1α Promoter and Its Transcriptional Inhibition by a Benzo[c]phenanthridine Derivative
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- 作者：Han Chen ; Haitao Long ; Xiaojie Cui ; Jiang Zhou ; Ming Xu ; Gu Yuan
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：February 12, 2014
- 年：2014
- 卷：136
- 期：6
- 页码：2583-2591
- 全文大小：506K
- ISSN：1520-5126
文摘
Four putative G-quadruplex sequences (PGSs) in the HIF1伪 promoter and the 5鈥睻TR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD, FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex (S1) has been proven to inhibit HIF1伪 transcription by blocking AP2 binding. A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and induce its conformational conversion from antiparallel to parallel orientation. The transcriptional suppression of HIF1伪 by this compound was demonstrated using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings provided a novel strategy for HIF1伪 regulation and potential insight for cancer therapy.