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| Status |
Public on Sep 04, 2019 |
| Title |
Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
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| Overall design |
LRT2/2B elements were silenced in K562 and OCI-AML3 cell lines by CRISPRi with 4 sgRNAs, using the empty sgRNA vector as a control. RNA-seq libraries were generated.
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| Contributor(s) |
Deniz O, Ahmed M, Todd CD, Dawson MA, Branco MR |
| Citation(s) |
32665538 |
| Submission date |
Sep 03, 2019 |
| Last update date |
Jul 27, 2020 |
| Contact name |
Miguel R Branco |
| E-mail(s) |
m.branco@qmul.ac.uk
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| Organization name |
Blizard Institute
|
| Street address |
4 Newark Street
|
| City |
London |
| ZIP/Postal code |
E1 2AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE136764 |
Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia |
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| Relations |
| BioProject |
PRJNA563622 |
| SRA |
SRP220125 |
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