ArticleNucleic acids research2014
HRAS is silenced by two neighboring G-quadruplexes and activated by MAZ, a zinc-finger transcription factor with DNA unfolding property.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 113 citations in OpenAlex.
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Variation and selection at predicted G-quadruplexes across the human pangenome.bioRxiv : the preprint server for biology · 2026Article
- CRISPR-Cas9 targeting of G-Quadruplex DNA in ADH1 promoter highlights its role in transcriptome and metabolome regulation.Nucleic acids research · 2025Article
- Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma.Archives of toxicology · 2024Article
- G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis.Nature communications · 2024Article
- G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis.Brain : a journal of neurology · 2023Article
- In vivo dynamics and regulation of DNA G-quadruplex structures in mammals.Cell & bioscience · 2023Review
- Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.Angewandte Chemie (International ed. in English) · 2023Article
- G4-interacting proteins endangering genomic stability at G4 DNA-forming sites.Biochemical Society transactions · 2023Article
- The Intertwined Role of 8-oxodG and G4 in Transcription Regulation.International journal of molecular sciences · 2023Review
- G-quadruplexes and associated proteins in aging and Alzheimer's disease.Frontiers in aging · 2023Review
- Article
- CpG Methylation Altered the Stability and Structure of the i-Motifs Located in the CpG Islands.International journal of molecular sciences · 2022Article
- G4-quadruplex-binding proteins: review and insights into selectivity.Biophysical reviews · 2022Review
- OGG1 in Lung-More than Base Excision Repair.Antioxidants (Basel, Switzerland) · 2022Review
- Major Achievements in the Design of Quadruplex-Interactive Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Drug discovery of small molecules targeting the higher-order hTERT promoter G-quadruplex.PloS one · 2022Article
- A Quantitative Proteomic Approach for the Identification of DNA Guanine Quadruplex-Binding Proteins.Journal of proteome research · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HRAS promoter contains immediately upstream of the transcription start site two neighboring G-elements, each capable of folding into a G-quadruplex structure. We have previously found that these G-quadruplexes bind to the zinc-finger transcription factors MAZ and Sp1. In the present study we have examined the interaction between the HRAS promoter and MAZ, demonstrating for the first time that the protein unfolds the G-quadruplex structures. We also demonstrate that MAZ-GST, in the presence of the complementary strands, promotes a rapid transformation of the two HRAS quadruplexes into duplexes. By a mutational analysis of the HRAS G-elements, we dissected the MAZ-binding sites from the quadruplex-forming motifs, finding that the two neighboring G-quadruplexes bring about a dramatic repression of transcription, in a synergistic manner. We also discovered that the two G-quadruplexes are strong targets for small anticancer molecules. We found that a cell-penetrating anthratiophenedione (ATPD-1), which binds tightly to the G-quadruplexes (ΔT > 15°C), promotes the total extinction of HRAS transcription. In contrast, when one of the two G-quadruplexes was abrogated by point mutations, ATPD-1 repressed transcription by only 50%. Our study provides relevant information for the rationale design of targeted therapy drugs specific for the HRAS oncogene.
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