G-Quadruplex Superstructure in the hTERT Core Promoter: Stabilization by Monomer Self-Stacking

Emanuela Micheli, Matteo Martufi, A. Galati, M. Franceschin, P. Santis, M. Savino, S. Cacchione
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Abstract

G-quadruplex-forming are widespread in eukaryotic genomes. In particular, G-quadruplex motifs have been found in the promoter region of 40% human genes. One of these genes is hTERT, encoding the catalytic subunit of human telomerase, whose up-regulated expression is responsible for the unlimited proliferative potential of most cancer cells. hTERT core promoter exhibits a high potential for G-quadruplex formation, containing nine partially overlapping PQS (putative quadruplex sequence) in a G-rich region of 68 nucleotides. Here we show the formation of a superstructure in the hTERT promoter deriving from the simultaneous folding of three adjacent G-quadruplex structures. Interestingly, G-quadruplex ligands are able to stabilize hTERT G-quadruplex structures and to alter transcription from the hTERT promoter, suggesting that the formation of a G-quadruplex superstructure could play a role in regulating gene transcription
hTERT核心助剂中的g -四联超结构:单体自堆积稳定化
g -四聚体形成在真核生物基因组中广泛存在。特别是,在40%的人类基因的启动子区域发现了g -四重基序。其中一个基因是hTERT,编码人类端粒酶的催化亚基,其上调表达是大多数癌细胞无限增殖潜力的原因。hTERT核心启动子显示出g -四重体形成的高潜力,在68个核苷酸的g -富区包含9个部分重叠的PQS(假定的四重体序列)。在这里,我们展示了hTERT启动子中由三个相邻的g -四重结构同时折叠而形成的上层结构。有趣的是,g -四重体配体能够稳定hTERT g -四重体结构并改变hTERT启动子的转录,这表明g -四重体上层结构的形成可能在调节基因转录中发挥作用
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