Journal article

Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia

Ozgen Deniz, Mamataz Ahmed, Christopher D Todd, Ana Rio-Machin, Mark A Dawson, Miguel R Branco

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Acute myeloid leukemia (AML) is characterised by a series of genetic and epigenetic alterations that result in deregulation of transcriptional networks. One understudied source of transcriptional regulators are transposable elements (TEs), whose aberrant usage could contribute to oncogenic transcriptional circuits. However, the regulatory influence of TEs and their links to AML pathogenesis remain unexplored. Here we identify six endogenous retrovirus (ERV) families with AML-associated enhancer chromatin signatures that are enriched in binding of key regulators of hematopoiesis and AML pathogenesis. Using both locus-specific genetic editing and simultaneous epigenetic silencing of multiple E..

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Grants

Awarded by Barts Charity


Awarded by People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant


Awarded by Sir Henry Dale Fellowship - Wellcome Trust


Awarded by Sir Henry Dale Fellowship - Royal Society


Awarded by European Union


Awarded by QMUL Research


Funding Acknowledgements

We thank Yasmine Benbrahim for ideas informing bioinformatic analyses, the Dawson lab for their guidance in lentiviral transduction of AML cell lines, Brian Huntly for providing OCI-AML3, MOLM-13 and HL-60 cell lines, Gary Warnes for flow cytometry analysis and Diego Villar and Jenny Frost for critical reading of the paper. This work was supported by funding from Barts Charity (Small Project Grants-MGU0462). O.D. received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765. M.R.B. was supported by a Sir Henry Dale Fellowship (101225/Z/13/Z), jointly funded by the Wellcome Trust and the Royal Society. This study makes use of data generated by the Blueprint Consortium. A full list of the investigators who contributed to the generation of the data is available from www.blueprint-epigenome.eu.Funding for the project was provided by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 282510-BLUEPRINT. This research utilised Queen Mary's Apocrita HPC facility, supported by QMUL Research-IT67.