Yuqi Chen, Angela Simeone, Larry Melidis, Sergio Martinez Cuesta, David Tannahill and Shankar Balasubramanian*,
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引用次数: 0
Abstract
Four-stranded G-quadruplexes (G4s) are DNA secondary structures that can form in the human genome. G4 structures have been detected in gene promoters and are associated with transcriptionally active chromatin and the recruitment of transcription factors and chromatin remodelers. We adopted a controlled, synthetic biology approach to understand how G4s can influence transcription. We stably integrated G4-forming sequences into the promoter of a synthetic reporter gene and inserted these into the genome of human cells. The integrated G4 sequences were shown to fold into a G4 structure within a cellular genomic context. We demonstrate that G4 structure formation within a gene promoter stimulates transcription compared to the corresponding G4-negative control promoter in a way that is not dependent on primary sequence or inherent G-richness. Systematic variation in the stability of folded G4s showed that in this system, transcriptional levels increased with higher stability of the G4 structure. By creating and manipulating a chromosomally integrated synthetic promoter, we have shown that G4 structure formation in a defined gene promoter can cause gene transcription to increase, which aligns with earlier observational correlations reported in the literature linking G4s to active transcription.
期刊介绍:
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
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