Dual Functions of Histone-Lysine N-Methyltransferase Setdb1 Protein at Promyelocytic Leukemia-Nuclear Body (PML-NB) MAINTAINING PML-NB STRUCTURE AND REGULATING THE EXPRESSION OF ITS ASSOCIATED GENES
Dual Functions of Histone-Lysine N-Methyltransferase Setdb1 Protein at Promyelocytic Leukemia-Nuclear Body (PML-NB) MAINTAINING PML-NB STRUCTURE AND REGULATING THE EXPRESSION OF ITS ASSOCIATED GENES
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DOI：
10.1074/jbc.m111.248534
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发表时间：
2011-11-25
影响因子：
4.8
通讯作者：
Kang, Yong-Kook
中科院分区：
文献类型：
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作者：
Cho, Sunwha;Park, Jung Sun;Kang, Yong-Kook
Setdb1/Eset是一种组蛋白H3赖氨酸9（H3K9）特异性甲基转移酶，与各种转录因子相关，通过染色质重塑调节基因表达。在这里，我们报告说，Setdb1与早幼粒细胞白血病（Pm 1）蛋白从小鼠发育的早期阶段，是早幼粒细胞白血病（PML）核小体（PML-NBs），已被链接到许多细胞过程，如凋亡，DNA损伤反应和转录调控的组成成员。砷处理，诱导Pm 1降解，导致Setdb1信号消失。Setdb1敲除导致PML-NB的重新定位。免疫沉淀结果表明Setdb1和Pm 1之间的物理相互作用。染色质免疫沉淀显示，在PML-NBs的框架内，Setdb1结合Id2的启动子并通过安装H3K9甲基化来抑制其表达。我们的研究结果表明，Setdb1执行双重的，但不可分割的，功能在PML-NB保持PML-NB的结构完整性和控制PML-NB相关基因的转录。
Setdb1/Eset is a histone H3 lysine 9 (H3K9)-specific methyltransferase that associates with various transcription factors to regulate gene expression via chromatin remodeling. Here, we report that Setdb1 associates with promyelocytic leukemia (Pm1) protein from the early stage of mouse development and is a constitutive member of promyelocytic leukemia (PML)-nuclear bodies (PML-NBs) that have been linked to many cellular processes such as apoptosis, DNA damage responses, and transcriptional regulation. Arsenic treatment, which induces Pm1 degradation, caused Setdb1 signals to disappear. Setdb1 knockdown resulted in dismantlement of PML-NBs. Immunoprecipitation results demonstrated physical interactions between Setdb1 and Pm1. Chromatin immunoprecipitation revealed that, within the frame of PML-NBs, Setdb1 binds the promoter of Id2 and suppresses its expression through installing H3K9 methylation. Our findings suggest that Setdb1 performs dual, but inseparable, functions at PML-NBs to maintain the structural integrity of PML-NBs and to control PML-NB-associated genes transcriptionally.