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Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer

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  • Fátima Valdés-Mora

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    St. Vincent’s Clinical School, UNSW Sydney)

  • Cathryn M. Gould

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Yolanda Colino-Sanguino

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Wenjia Qu

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Jenny Z. Song

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Kylie M. Taylor

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Fabian A. Buske

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Aaron L. Statham

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Shalima S. Nair

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    St. Vincent’s Clinical School, UNSW Sydney)

  • Nicola J. Armstrong

    (Murdoch University)

  • James G. Kench

    (Royal Prince Alfred Hospital
    University of Sydney
    Clinical Prostate Cancer Research Group, Cancer Division, Garvan Institute of Medical Research)

  • Kenneth M. L. Lee

    (University of Sydney
    Anatomical Pathology Department, Concord Hospital)

  • Lisa G. Horvath

    (University of Sydney
    Clinical Prostate Cancer Research Group, Cancer Division, Garvan Institute of Medical Research
    Chris O’Brien Lifehouse)

  • Minru Qiu

    (Sydpath, St Vincent’s Hospital)

  • Alexei Ilinykh

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • Nicole S. Yeo-Teh

    (Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research)

  • David Gallego-Ortega

    (St. Vincent’s Clinical School, UNSW Sydney
    Tumour Development Group. Cancer Division, Garvan Institute of Medical Research)

  • Clare Stirzaker

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    St. Vincent’s Clinical School, UNSW Sydney)

  • Susan J. Clark

    (Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research
    St. Vincent’s Clinical School, UNSW Sydney)

Abstract

Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.

Suggested Citation

  • Fátima Valdés-Mora & Cathryn M. Gould & Yolanda Colino-Sanguino & Wenjia Qu & Jenny Z. Song & Kylie M. Taylor & Fabian A. Buske & Aaron L. Statham & Shalima S. Nair & Nicola J. Armstrong & James G. Ke, 2017. "Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01393-8
    DOI: 10.1038/s41467-017-01393-8
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