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

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. Kench, Kenneth M. L. Lee, Lisa G. Horvath, Minru Qiu, Alexei Ilinykh, Nicole S. Yeo-Teh, David Gallego-Ortega, Clare Stirzaker and Susan J. Clark ()
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Fátima Valdés-Mora: Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
Cathryn M. Gould: Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research
Yolanda Colino-Sanguino: Histone Variants Group, 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
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
Nicola J. Armstrong: Murdoch University
James G. Kench: Royal Prince Alfred Hospital
Kenneth M. L. Lee: University of Sydney
Lisa G. Horvath: University of Sydney
Minru Qiu: Sydpath, St Vincent’s Hospital
Alexei Ilinykh: Histone Variants Group, 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
David Gallego-Ortega: St. Vincent’s Clinical School, UNSW Sydney
Clare Stirzaker: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research
Susan J. Clark: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01393-8

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