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Regulation of PDGFR-β gene expression by targeting the G-vacancy bearing G-quadruplex in promoter
- Source :
- Nucleic Acids Research
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
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.
- Subjects :
- Porphyrins
Base Sequence
AcademicSubjects/SCI00010
DNA, Single-Stranded
Promoter
DNA
Biology
G-quadruplex
Footprinting
Cell biology
G-Quadruplexes
Receptor, Platelet-Derived Growth Factor beta
chemistry.chemical_compound
Chemical Biology and Nucleic Acid Chemistry
Gene Expression Regulation
chemistry
Transcription (biology)
Gene expression
Genetics
Humans
DNA supercoil
Promoter Regions, Genetic
Gene
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....9d5608f6e16b0b47b8e5785945ec591f