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| Status |
Public on Feb 06, 2024 |
| Title |
G-quadruplex DNA structure is a positive regulator of MYC transcription |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
DNA structure can regulate genome function. Four-stranded DNA G-quadruplex (G4) structures have been implicated in transcriptional regulation; however, previous studies have not directly addressed the role of an individual G4 within its endogenous cellular context. Using CRISPR to genetically abrogate endogenous G4 structure folding, we directly interrogate the G4 found within the upstream regulatory region of the critical human MYC oncogene. G4 loss leads to suppression of MYC transcription from the P1 promoter that is mediated by the deposition of a de novo nucleosome alongside alterations in RNA polymerase recruitment. We also show that replacement of the endogenous MYC G4 with a different G4 structure from the KRAS oncogene restores G4 folding and MYC transcription. Moreover, we demonstrate that the MYC G4 structure itself, rather than its sequence, recruits transcription factors and histone modifiers. Overall, our work establishes that G4 structures are important features of transcriptional regulation that coordinate recruitment of key chromatin proteins and the transcriptional machinery through interactions with DNA secondary structure, rather than primary sequence.
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| Overall design |
Expression profiling by high throughput sequencing. Genome binding/occupancy profiling by high throughput sequencing
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| Web link |
https://www.pnas.org/doi/10.1073/pnas.2320240121
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| Contributor(s) |
Esain-Garcia I, Kirchner A, Melidis L, Araujo Tavares RD, Dhir S, Simeone A, Yu Z, Madden SK, Hermann R, Tannahill D, Balasubramanian S |
| Citation(s) |
38315865 |
| Submission date |
Jan 20, 2023 |
| Last update date |
Feb 07, 2024 |
| Contact name |
Larry Melidis |
| E-mail(s) |
lm512@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
CRUK-CI
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| Lab |
Balasubramanian
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| Street address |
Robinson Way
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| City |
Cambridge |
| State/province |
Not US or Canada |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
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| Platforms (3) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
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| Samples (243)
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| Relations |
| BioProject |
PRJNA925884 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223370_RAW.tar |
47.5 Gb |
(http)(custom) |
TAR (of BW, TXT) |
| GSE223370_reviewed.xlsx |
171.9 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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