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- W3215089213 abstract "G-quadruplex is an essential element in gene transcription that serves as a promising drug target. Guanine-vacancy-bearing G-quadruplex (GVBQ) is a newly identified G-quadruplex that has distinct structural features from the canonical G-quadruplex. Potential GVBQ-forming motifs are widely distributed in gene promoter regions. However, whether GVBQ can form in genomic DNA and be an effective target for manipulating gene expression is unknown. Using photo-crosslinking, dimethyl sulfate footprinting, exonuclease digestion and in vitro transcription, we demonstrated the formation of a GVBQ in the G-rich nuclease hypersensitivity element within the human PDGFR-β gene promoter region in both single-stranded and double-stranded DNA. The formation of GVBQ in dsDNA could be induced by negative supercoiling created by downstream transcription. We also found that the PDGFR-β GVBQ was specifically recognized and stabilized by a new synthetic porphyrin guanine conjugate (mPG). Targeting the PDGFR-β GVBQ in human cancer cells using the mPG could specifically alter PDGFR-β gene expression. Our work illustrates that targeting GVBQ with mPG in human cells can regulate the expression level of a specific gene, thus indicating a novel strategy for drug development." @default.
- W3215089213 created "2021-12-06" @default.
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- W3215089213 date "2021-11-30" @default.
- W3215089213 modified "2023-10-15" @default.
- W3215089213 title "Regulation of PDGFR-β gene expression by targeting the G-vacancy bearing G-quadruplex in promoter" @default.
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- W3215089213 doi "https://doi.org/10.1093/nar/gkab1154" @default.
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