Mi Wenyi, Guan Haipeng, Lyu Jie, Zhao Dan, Xi Yuanxin, Jiang Shiming, Andrews Forest H, Wang Xiaolu, Gagea Mihai, Wen Hong, Tora Laszlo, Dent Sharon Y R, Kutateladze Tatiana G, Li Wei, Li Haitao, Shi Xiaobing
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2017 Oct 20;8(1):1088. doi: 10.1038/s41467-017-01173-4.
Recognition of modified histones by "reader" proteins constitutes a key mechanism regulating diverse chromatin-associated processes important for normal and neoplastic development. We recently identified the YEATS domain as a novel acetyllysine-binding module; however, the functional importance of YEATS domain-containing proteins in human cancer remains largely unknown. Here, we show that the YEATS2 gene is highly amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell growth and survival. YEATS2 binds to acetylated histone H3 via its YEATS domain. The YEATS2-containing ATAC complex co-localizes with H3K27 acetylation (H3K27ac) on the promoters of actively transcribed genes. Depletion of YEATS2 or disruption of the interaction between its YEATS domain and acetylated histones reduces the ATAC complex-dependent promoter H3K9ac levels and deactivates the expression of essential genes. Taken together, our study identifies YEATS2 as a histone H3K27ac reader that regulates a transcriptional program essential for NSCLC tumorigenesis.
“读取器”蛋白对修饰组蛋白的识别构成了一种关键机制，可调节对正常和肿瘤发育至关重要的多种与染色质相关的过程。我们最近将YEATS结构域鉴定为一种新型乙酰赖氨酸结合模块；然而，含YEATS结构域的蛋白在人类癌症中的功能重要性仍 largely unknown。在这里，我们表明YEATS2基因在人类非小细胞肺癌（NSCLC）中高度扩增，并且是癌细胞生长和存活所必需的。YEATS2通过其YEATS结构域与乙酰化组蛋白H3结合。含YEATS2的ATAC复合物与H3K27乙酰化（H3K27ac）在活跃转录基因的启动子上共定位。YEATS2的缺失或其YEATS结构域与乙酰化组蛋白之间相互作用的破坏会降低ATAC复合物依赖性启动子H3K9ac水平，并使必需基因的表达失活。综上所述，我们的研究将YEATS2鉴定为一种组蛋白H3K27ac读取器，其调节NSCLC肿瘤发生所必需的转录程序。
Zotero 插件
