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

被引：62

作者：

Valdes-Mora, Fatima ^{[1
,2
,3
]}

Gould, Cathryn M. ^{[1
,2
]}

Colino-Sanguino, Yolanda ^{[1
,2
]}

Qu, Wenjia ^{[2
]}

Song, Jenny Z. ^{[2
]}

Taylor, Kylie M. ^{[1
,2
]}

Buske, Fabian A. ^{[2
]}

Statham, Aaron L. ^{[2
]}

Nair, Shalima S. ^{[2
,3
]}

Armstrong, Nicola J. ^{[4
]}

Kench, James G. ^{[5
,6
,7
]}

Lee, Kenneth M. L. ^{[6
,8
]}

Horvath, Lisa G. ^{[6
,7
,9
]}

Qiu, Minru ^{[10
]}

Ilinykh, Alexei ^{[1
,2
]}

Yeo-Teh, Nicole S. ^{[1
,2
]}

Gallego-Ortega, David ^{[3
,11
]}

Stirzaker, Clare ^{[2
,3
]}

Clark, Susan J. ^{[2
,3
]}

机构：

[1] Garvan Inst Med Res, Histone Variants Grp, Genom & Epigenet Div, Sydney, NSW 2010, Australia

[2] Garvan Inst Med Res, Epigenet Res Lab, Genom & Epigenet Div, Sydney, NSW 2010, Australia

[3] UNSW Sydney, St Vincents Clin Sch, Sydney, NSW 2010, Australia

[4] Murdoch Univ, Math & Stat, Perth, WA 6150, Australia

[5] Royal Prince Alfred Hosp, Dept Tissue Pathol & Diagnost Oncol, Camperdown, NSW 2050, Australia

[6] Univ Sydney, Sydney Med Sch, Sydney, NSW 2050, Australia

[7] Garvan Inst Med Res, Canc Div, Clin Prostate Canc Res Grp, Sydney, NSW 2010, Australia

[8] Concord Hosp, Anat Pathol Dept, Sydney, NSW 2139, Australia

[9] Chris OBrien Lifehouse, Sydney, NSW 2050, Australia

[10] St Vincents Hosp, Dept Anat Pathol, Sydpath, Sydney, NSW 2010, Australia

[11] Garvan Inst Med Res, Canc Div, Tumour Dev Grp, Sydney, NSW 2010, Australia

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国医学研究理事会;

关键词：

NUCLEOSOME-DEPLETED REGIONS; ANDROGEN RECEPTOR; DNA METHYLATION; GENE; TRANSCRIPTION; CHROMATIN; PROLIFERATION; FRAMEWORK; EFFICIENT; DYNAMICS;

D O I：

10.1038/s41467-017-01393-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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