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

Author

Listed:
  • Özgen Deniz

    (Barts and The London School of Medicine and Dentistry
    Life Sciences Institute)

  • Mamataz Ahmed

    (Barts and The London School of Medicine and Dentistry
    Life Sciences Institute)

  • Christopher D. Todd

    (Barts and The London School of Medicine and Dentistry
    Life Sciences Institute
    Babraham Institute)

  • Ana Rio-Machin

    (Life Sciences Institute
    Barts Cancer Institute)

  • Mark A. Dawson

    (Peter MacCallum Cancer Center)

  • Miguel R. Branco

    (Barts and The London School of Medicine and Dentistry
    Life Sciences Institute)

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 ERVs, we demonstrate that ERV deregulation directly alters the expression of adjacent genes in AML. Strikingly, deletion or epigenetic silencing of an ERV-derived enhancer suppresses cell growth by inducing apoptosis in leukemia cell lines. This work reveals that ERVs are a previously unappreciated source of AML enhancers that may be exploited by cancer cells to help drive tumour heterogeneity and evolution.

Suggested Citation

  • Özgen Deniz & Mamataz Ahmed & Christopher D. Todd & Ana Rio-Machin & Mark A. Dawson & Miguel R. Branco, 2020. "Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17206-4
    DOI: 10.1038/s41467-020-17206-4
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    Cited by:

    1. Sophia Groh & Anna Viktoria Milton & Lisa Katherina Marinelli & Cara V. Sickinger & Angela Russo & Heike Bollig & Gustavo Pereira de Almeida & Andreas Schmidt & Ignasi Forné & Axel Imhof & Gunnar Scho, 2021. "Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Chunhong Yu & Xiaoyun Lei & Fang Chen & Song Mao & Lu Lv & Honglu Liu & Xueying Hu & Runhan Wang & Licong Shen & Na Zhang & Yang Meng & Yunfan Shen & Jiale Chen & Pishun Li & Shi Huang & Changwei Lin , 2022. "ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Konsta Karttunen & Divyesh Patel & Jihan Xia & Liangru Fei & Kimmo Palin & Lauri Aaltonen & Biswajyoti Sahu, 2023. "Transposable elements as tissue-specific enhancers in cancers of endodermal lineage," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Xuemeng Zhou & Tsz Wing Sam & Ah Young Lee & Danny Leung, 2021. "Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

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