The role of CpG methylation in cell type-specific expression of the aquaporin-5 gene
The role of CpG methylation in cell type-specific expression of the aquaporin-5 gene
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DOI：
10.1016/j.bbrc.2006.12.126
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发表时间：
2007-02-23
影响因子：
3.1
通讯作者：
Isohama, Yoichiro
中科院分区：
文献类型：
--
作者：
Nomura, Johji;Hisatsune, Akinori;Isohama, Yoichiro
水通道蛋白-5（AQP 5）以细胞类型特异性方式表达。在这里，我们表明，AQP 5基因的调控CpG甲基化。在NIH-3 T3或新鲜分离的肺泡上皮细胞中，含有假定的CpG岛的AQP 5启动子高度甲基化，与这些细胞中该基因的抑制相关。相比之下，AQP 5启动子在MLE-12或培养的肺泡上皮细胞中低甲基化，其表达高水平的AQP 5。5-氮杂胞苷可解除NIH-3 T3细胞中AQP 5转录的抑制，并且AQP 5启动子的体外甲基化导致MLE-12细胞中报告基因转录的抑制。染色质免疫沉淀分析表明，内源性Sp1绑定到低甲基化，但不是高度甲基化，AQP 5启动子区域。这些结果表明，低甲基化状态的AQP 5启动子，导致增加的Sp1结合可能发挥作用，在调节细胞类型特异性表达的AQP 5基因。(c)2006年爱思唯尔公司All rights reserved.
Aquaporin-5 (AQP5) is expressed in a cell type-specific manner. Here, we show that the AQP5 gene is regulated by CpG methylation. The AQP5 promoter containing a putative CpG island was highly methylated in NIH-3T3 or freshly isolated alveolar epithelial cells, correlating with the repression of this gene in these cells. In contrast, the AQP5 promoter was hypo-methylated in MLE-12 or cultured alveolar epithelial cells, which express high levels of AQP5. Repression of AQP5 transcription in NIH-3T3 cells could be relieved with 5-azacytidine, and in vitro methylation of the AQP5 promoter resulted in inhibition of transcription of the reporter gene in MLE-12 cells. Chromatin immunoprecipitation assays showed that endogenous Sp1 bound to the hypo-methylated, but not highly methylated, AQP5 promoter region. These results demonstrate that the hypo-methylated state of the AQP5 promoter leading to increased Sp1 binding may play a role in regulation of cell type-specific expression of the AQP5 gene. (c) 2006 Elsevier Inc. All rights reserved.