G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD
| Autor: | Lucas T. Gray, Aarthy C. Vallur, Johanna Eddy, Nancy Maizels |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetic Vectors
G-quadruplex Article Cell Line chemistry.chemical_compound Capillary Electrochromatography Transcriptional regulation Humans Point Mutation Binding site Molecular Biology Gene Xeroderma Pigmentosum Group D Protein Genetics Genome biology DNA Helicases Helicase Promoter DNA Sequence Analysis DNA Cell Biology Microarray Analysis 3. Good health DNA-Binding Proteins G-Quadruplexes genomic DNA Gene Expression Regulation chemistry biology.protein RNA Sequence Alignment Signal Transduction |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| DOI: | 10.1038/nchembio.1475 |
| Popis: | G4 motifs are greatly enriched near promoters, suggesting that quadruplex structures may be targets of transcriptional regulation. Here we show, by ChIP-Seq analysis of human cells, that 40% of the binding sites of the transcription-associated helicases, XPB and XPD, overlap with G4 motifs. The highly significant overlap of XPB and XPD binding sites with G4 motifs cannot be explained by GC-richness or parameters of the genomewide analysis, but instead suggests that these proteins are recruited to quadruplex structures that form in genomic DNA (G4 DNA). Biochemical analysis demonstrates that XPD is a robust G4 DNA helicase, and XPB binds to G4 DNA. XPB and XPD are enriched near the transcription start site (TSS) at 20% of genes, especially highly transcribed genes. XPB and XPD enrichment at G4 motifs characterizes specific signaling pathways and regulatory pathways associated with specific cancers. These results identify new candidate pathways for therapies targeted to quadruplexes. |
| Databáze: | OpenAIRE |
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