DNMT1与MBD4协同作用，抑制人T细胞中糖皮质激素诱导的TNFR相关蛋白的表达。
DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid-induced TNFR-related protein in human T cells.
作者信息
Wang Shuaiwei, Li Yangyang, Zhu Fangming, Lin Fang, Luo Xuerui, Zhao Binbin, Zhang Peng, Li Dan, Gao Yayi, Liang Rui, Liu Luyan, Tsun Andy, Yuan Xiaojun, Wu Kejin, Li Bin
机构信息
Shanghai Key Laboratory of Bio-energy Crops, School of Life Science, Shanghai University, China.
Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, China.
出版信息
FEBS Lett. 2017 Jul;591(13):1929-1939. doi: 10.1002/1873-3468.12690. Epub 2017 Jun 10.
Glucocorticoid-induced TNFR-related protein (GITR) is constitutively expressed in T regulatory (Treg) cells and regulates their suppressive function. We identified two methylated CpG islands in the Gitr locus. Using a ChIP assay, we demonstrate that both DNMT1 and methyl-CpG-binding domain Protein 4 (MBD4) bind to the Gitr promoter. Moreover, knockdown of DNMT1 decreases the binding activity of MBD4. We observed much higher levels of both DNMT1 and MBD4 in human CD4 CD25 conventional T (Tconv) cells. Moreover, co-overexpression of DNMT1 and MBD4 in Treg cells significantly inhibits GITR expression and impairs their suppressive activity. Our results reveal a novel molecular mechanism by which MBD4 inhibits GITR expression in a DNMT1-dependent manner.
糖皮质激素诱导的肿瘤坏死因子受体相关蛋白（GITR）在调节性T（Treg）细胞中组成性表达，并调节其抑制功能。我们在Gitr基因座中鉴定出两个甲基化的CpG岛。使用染色质免疫沉淀（ChIP）试验，我们证明DNA甲基转移酶1（DNMT1）和甲基-CpG结合域蛋白4（MBD4）都与Gitr启动子结合。此外，DNMT1的敲低降低了MBD4的结合活性。我们观察到在人CD4 CD25常规T（Tconv）细胞中DNMT1和MBD4的水平都高得多。此外，在Treg细胞中共同过表达DNMT1和MBD4会显著抑制GITR表达并损害其抑制活性。我们的结果揭示了一种新的分子机制，即MBD4以DNMT1依赖的方式抑制GITR表达。
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