Histone Variants Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Nat Commun. 2017 Nov 7;8(1):1346. doi: 10.1038/s41467-017-01393-8.
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.
组蛋白变体 H2A.Z（H2A.Zac）乙酰化发生在活性启动子上，并与前列腺癌中癌基因的激活有关，但它在增强子功能中的作用仍知之甚少。在这里，我们表明，含有 H2A.Zac 的核小体通常重新分布到癌症中的新增强子，导致染色质可及性和异位基因表达的同时获得。值得注意的是，乙酰化 H2A.Z 核小体的掺入是激活雄激素受体 (AR) 相关增强子的先决条件。H2A.Zac 核小体占据迅速重塑，以侧翼 AR 位点，启动无核小体区域的形成，并在雄激素处理后产生 AR-增强子 RNA。值得注意的是，更高水平的全局 H2A.Zac 与更差的预后相关。总的来说，这些数据表明 H2A.Zac 在激活前列腺癌中新形成的增强子方面具有新的作用。
