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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells
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SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

机译：SETD6控制雌激素响应基因的表达和乳腺癌细胞的增殖

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摘要

The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signaling. Specifically, SETD6 associates with the estrogen receptor alpha (ER alpha), histone deacetylase HDAC 1, metastasis protein MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC 1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signaling and cellular proliferation.
机译：赖氨酸甲基转移酶SETD6修饰了组蛋白变体H2AZ，它是核受体依赖性转录的关键成分。在这里，我们报告鉴定与SETD6相关联的几个因素，并与核激素受体信号传导有关。具体来说，SETD6与雌激素受体α（ER alpha），组蛋白脱乙酰基酶HDAC 1，转移蛋白MTA2和转录共激活因子TRRAP相关。萤光素酶报告基因检测将SETD6鉴定为转录阻遏物，与它与HDAC 1和MTA2的关联一致。但是，SETD6充当了几个雌激素反应性基因（例如PGR和TFF1）的共激活因子。与这些结果一致，在几种乳腺癌细胞系中SETD6的沉默导致细胞增殖缺陷，并伴随着细胞周期抑制剂CDKN1A表达的增强和细胞凋亡的诱导。在本文中，我们已经鉴定了几种与SETD6相关的染色质蛋白，并将SETD6描述为核受体信号传导和细胞增殖的必要因子。

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