Cell-specific epigenetic regulation of ChM-I gene expression: Crosstalk between DNA methylation and histone acetylation
Cell-specific epigenetic regulation of ChM-I gene expression: Crosstalk between DNA methylation and histone acetylation
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DOI：
10.1016/j.bbrc.2007.10.135
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发表时间：
2008-01-04
影响因子：
3.1
通讯作者：
Toguchida, Junya
中科院分区：
文献类型：
--
作者：
Aoyama, Tomoki;Okamoto, Takeshi;Toguchida, Junya
软骨调节素-I（chondromodulin-I，ChM-I）基因是软骨特异性基因，其表达受Sp3与核心启动子区结合的调控，而Sp3的结合受成骨细胞系骨肉瘤（osteosarcoma，OS）靶基因组中CpG甲基化的抑制。在3个ChM-I阴性OS细胞系中，与ChM-I基因的高甲基化启动子区相关的组蛋白尾部被组蛋白去乙酰化酶2（HDAC 2）去乙酰化。用HDAC抑制剂处理诱导了一个细胞系中Sp3的结合，该细胞系变为ChM-I阳性。该过程与乙酰化而不是历史H3在赖氨酸9（H3-K9）处的二甲基化相关，并且令人惊讶地与核心启动子区域的去甲基化相关。去甲基化是短暂的，并在组蛋白去乙酰化快速恢复后逐渐被甲基化取代。这些结果代表了分化的可塑性受到细胞特异性可塑性表观遗传调控的调节的一个例子。(c)2007爱思唯尔公司All rights reserved.
The expression of the chondromodulin-I (ChM-I) gene, a cartilage-specific gene, is regulated by the binding of Sp3 to the core promoter region, which is inhibited by the methylation of CpG in the target genome in the osteogenic lineage, osteosarcoma (OS) cells. The histone tails associated with the hypermethylated promoter region of the ChM-I gene were deacetylated by histone deacetylase 2 (HDAC2) in three ChM-I-negative OS cell lines. Treatment with an HDAC inhibitor induced the binding of Sp3 in one cell line, which became ChM-I-positive. This process was associated with acetylation instead of the dimethylation of historic H3 at lysine 9 (H3-K9) and, surprisingly, the demethylation of the core promoter region. The demethylation was transient, and gradually replaced by methylation after a rapid recovery of histone deacetylaion. These results represent an example of the plasticity of differentiation being regulated by the cell-specific plasticity of epigenetic regulation. (c) 2007 Elsevier Inc. All rights reserved.