下游转录远程诱导人类端粒酶催化亚基（hTERT）基因启动子形成G-四链体

DNA will form G-quadruplex when it bears several guanine tracts (G-tract). G-quadruplex forming sequences are concentrated in promoters in the genome of many species. The catalytic subunit of human telomerase, hTERT, is highly expressed in some cancer cells. hTERT promoter which contains G-quadruplex forming sequence is mutant in about 75% of glioblastoma and malignant. These mutation will significantly weaken G-quadruplex formation. In our research, we found that the downstream transcription induce the formation of G-quadruplex in hTERT promoter. Our project will focus on the influence factors of structure formation, structure in cells and the interaction of protein and the structure. This study will improve the G-quadruplex formation mechanism in transcription, and analysis the biological function of the G-quadrplex in hTERT promoter.

富含碱基 G 的核酸能够形成 G-四链体结构。在很多物种的基因组上，G-四链体形成序列在基因的启动子区域富集。人类端粒酶催化亚基hTERT是端粒酶的组成部分，该基因在癌细胞中高表达。hTERT基因的启动子区域含有一段能够形成G-四链体结构的序列，约75%的胶质母细胞瘤和恶性黑色素瘤的DNA在这一区域发生突变，这些突变会明显的减弱G-四链体结构的形成。我们在研究中发现，下游转录会远程诱导hTERT基因的启动子形成G-四链体结构。本项目将围绕hTERT启动子区形成G-四链体结构展开研究，我们将分别对影响结构形成的因素、结构在细胞内的形成、结构形成对蛋白与DNA相互作用的影响几方面进行探讨。该研究将进一步完善G-四链体结构在转录中的形成机制，并且解析hTERT启动子区形成G-四链体的生物学功能。