Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, 113 Gwahangno, Yuseong-gu, 305-806 Daejeon, South Korea.
J Biol Chem. 2011 Nov 25;286(47):41115-24. doi: 10.1074/jbc.M111.248534. Epub 2011 Sep 14.
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 (Pml) 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 Pml degradation, caused Setdb1 signals to disappear. Setdb1 knockdown resulted in dismantlement of PML-NBs. Immunoprecipitation results demonstrated physical interactions between Setdb1 and Pml. 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.
Setdb1/Eset 是一种组蛋白 H3 赖氨酸 9（H3K9）特异性甲基转移酶，它与多种转录因子结合，通过染色质重塑来调节基因表达。在这里，我们报告 Setdb1 从早期的小鼠发育阶段开始与早幼粒细胞白血病（Pml）蛋白相关联，并且是早幼粒细胞白血病（Pml）核体（PML-NBs）的组成部分，PML-NBs 与许多细胞过程有关，如凋亡、DNA 损伤反应和转录调节。砷处理诱导 Pml 降解，导致 Setdb1 信号消失。Setdb1 的敲低导致 PML-NBs 的解体。免疫沉淀结果表明 Setdb1 和 Pml 之间存在物理相互作用。染色质免疫沉淀显示，在 PML-NBs 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 在 PML-NBs 上执行双重但不可分割的功能，以维持 PML-NBs 的结构完整性并控制 PML-NB 相关基因的转录。
