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| Status |
Public on Dec 14, 2022 |
| Title |
Multi-omics and machine learning reveal context-specific gene regulatory activities of PML-RARA in Acute Promyelocytic Leukemia [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The PML-RARA fusion protein is the hallmark driver of Acute Promyelocytic Leukemia (APL) and disrupts retinoic acid signaling, leading to wide-scale gene expression changes and uncontrolled proliferation of myeloid precursor cells. While known to be recruited to binding sites across the genome, its impact on gene regulation and expression is under-explored. Using integrated multi-omics datasets, we characterize the influence of PML-RARA binding on gene expression and regulation in an inducible cell line model and APL patient ex vivo samples. We find that genes whose regulatory elements recruit PML-RARA are not uniformly transcriptionally repressed, as commonly suggested, but also may be upregulated or remain unchanged. We develop a novel, computational machine learning application to deconvolute the complex, local transcription factor binding site environment at PML-RARA bound positions to reveal distinct signatures that modulate how PML-RARA directs the transcriptional response.
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| Overall design |
Application of RNA-seq to the U937-PR9 cell line system, before and after PML-RARA inuction. Application of RNA-seq to two ex vivo APL patient samples
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| Contributor(s) |
Villiers W, Dillon R, Mifsud B, Osborne C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
May 03, 2021 |
| Last update date |
Dec 14, 2022 |
| Contact name |
Cameron Osborne |
| E-mail(s) |
cameron.osborne@kcl.ac.uk
|
| Organization name |
King's College London
|
| Department |
Medical and Molecular Genetics
|
| Street address |
Guy's Hospital Campus
|
| City |
London |
| ZIP/Postal code |
SE1 9RT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE173755 |
Multi-omics and machine learning reveal context-specific gene regulatory activities of PML-RARA in Acute Promyelocytic Leukemia |
|
| Relations |
| BioProject |
PRJNA726969 |
| SRA |
SRP318229 |
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