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| Status |
Public on Feb 13, 2014 |
| Title |
Loss of imprinting at the CTCF binding sites in the DLK1-DIO3 domain reactivates microRNA expression in acute promyelocytic leukaemia |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
We report the DNA-methylation profiling of 10 regions selected from the DLK1-DIO3 domain on chromosome 14q32 in BM/PB samples from patients with acute promyelocytic leukaemia (APL), other subclasses of acute myeloid leukaemia and healthy donors, using high-throughput amplicon bisulfite sequencing with Roche 454 technology. We identify monoallelic-hypermethylation in APL only at the differentially methylated region (DMR) located upstream from the MEG3 gene (MEG3-DMR), whereas no changes in the DNA methylation profile were detected at the imprinting control region of the domain (IG-DMR) among the samples analysed. We show that the expression profile of 6 miRNAs clustered downstream from the MEG3-DMR correlates with the methylation profile at both DMRs. We demonstrate that miRNAs expression negatively correlates with DNA-methylation at the IG-DMR and MEG3 gene-body, whereas the correlation was positive for the CpGs located in the promoter of MEG3, including the binding sites for the insulator CTCF. We propose a loss of imprinting at the CTCF binding sites in patients with APL. These results are consistent with the previously reported DLK1-DIO3 miRNAs overexpression in APL, indicating a possible involvement of these ncRNAs in the pathogenesis of the disease.
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| |
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| Overall design |
Investigation of the epigenetic regulation of the miRNAs clustered in 14q32 by next-generation sequencing
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| Contributor(s) |
Manodoro F, Marzec J, Chaplin T, Wang J, Iqbal S, Gribben JG, Young BD, Debernardi S |
| Citation(s) |
24493669 |
| Submission date |
Nov 27, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Jacek Dariusz Marzec |
| E-mail(s) |
j.marzec@qmul.ac.uk
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| Organization name |
Barts Cancer Institute
|
| Department |
Centre for Haemato-Oncology
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| Lab |
Cancer Genomics
|
| Street address |
Charterhouse Square
|
| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL14603 |
454 GS FLX Titanium (Homo sapiens) |
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| Samples (47)
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| Relations |
| BioProject |
PRJNA182243 |
| SRA |
SRP017323 |
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