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Series GSE223370 Query DataSets for GSE223370
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
Genome binding/occupancy profiling by high throughput sequencing
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.
Overall design Expression profiling by high throughput sequencing. Genome binding/occupancy profiling by high throughput sequencing
Web link
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
Organization name University of Cambridge
Department CRUK-CI
Lab Balasubramanian
Street address Robinson Way
City Cambridge
State/province Not US or Canada
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (3)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (243)
GSM7815650 BG4_MUT_Bio1.Tech1
GSM7815651 BG4_MUT_Bio1.Tech2
GSM7815652 BG4_MUT_Bio2.Tech1
BioProject PRJNA925884

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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