RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1.
RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1.
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RFX1 通过招募组蛋白甲基转移酶 SUV39H1 调节狼疮 T 细胞中 CD70 和 CD11a 的表达
DOI：
10.1186/ar3214
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发表时间：
2010
影响因子：
4.9
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Zhao M;Wu X;Zhang Q;Luo S;Liang G;Su Y;Tan Y;Lu Q
调节因子X-box 1（RFX 1）可与DNA甲基转移酶1（DNMT 1）和组蛋白去乙酰化酶1（HDAC 1）相互作用，下调RFX 1可导致系统性红斑狼疮（SLE）患者CD 4 +T细胞分化簇（CD）11 a和CD 70启动子DNA低甲基化和组蛋白H3高乙酰化。这导致CD 11 a和CD 70过表达，从而引发自身免疫反应。为了进一步阐明SLE患者自身免疫相关基因失调的表观遗传学机制，我们研究了RFX 1是否参与调节SLE患者CD 4 +T细胞CD 11 a和CD 70启动子区组蛋白3赖氨酸9（H3 K9）三甲基化。通过染色质免疫沉淀（ChIP）和实时定量PCR测量H3 K9三甲基化水平。使用人T细胞核转染试剂盒用质粒转染CD 4 +T细胞。RFX 1和组蛋白甲基转移酶抑制剂杂色3-9（果蝇）同源物1（SUV 39 H1）的相互作用，通过免疫共沉淀（co-IP）和蛋白质印迹和免疫荧光染色。结果SLE患者CD 4 +T细胞中CD 11 a和CD 70启动子区H3 K9三甲基化水平显著降低。RFX 1与SUV 39 H1在健康对照CD 4 +T细胞中的CD 11 a和CD 70启动子处共免疫沉淀。结论RFX 1可将SUV 39 H1募集至CD 4 + T细胞中CD 11 a和CD 70基因启动子区，从而调节H3 K9三甲基化水平。这些发现进一步阐明了RFX 1下调在SLE中自身免疫基因的表观遗传去抑制中的核心作用。
IntroductionRegulatory factor X-box 1 (RFX1) can interact with DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), and RFX1 down-regulation contributes to DNA hypomethylation and histone H3 hyperacetylation at the cluster of differentiation (CD) 11a and CD70 promoters in CD4+T cells of patients with systemic lupus erythematosus (SLE). This leads to CD11a and CD70 overexpression, thereby triggering autoimmune responses. In order to provide more insight into the epigenetic mechanisms leading to the deregulation of autoimmune-related genes in SLE, we asked whether RFX1 is involved in regulating histone 3 lysine 9 (H3K9) tri-methylation at the CD11a and CD70 promoters in SLE CD4+T cells.MethodsCD4+T cell samples were isolated from 15 SLE patients and 15 healthy controls. H3K9 tri-methylation levels were measured by chromatin immunoprecipitation (ChIP) and real-time quantitative PCR. CD4+T cells were transfected with plasmids using the Human T cell Nucleofector Kit. RFX1 and histone methyltransferase suppressor of variegation 3-9 (Drosophila) homolog 1 (SUV39H1) interaction was determined by co-immunoprecipation (co-IP) and Western blot and immunofluorescence staining. CD11a and CD70 mRNA levels were measured by real-time RT-PCR.ResultsH3K9 tri-methylation levels were significantly reduced within the CD11a and CD70 promoter regions in SLE CD4+T cells. RFX1 co-immunoprecipitated with SUV39H1 at the CD11a and CD70 promoters in healthy control CD4+T cells. Overexpressing or knocking-down RFX1 revealed that RFX1 expression correlated with H3K9 tri-methylation levels, as well as CD11a and CD70 expression levels in CD4+T cells.ConclusionsRFX1 recruits SUV39H1 to the promoter regions of the CD11a and CD70 genes in CD4+T cells, thereby regulating local H3K9 tri-methylation levels. These findings shed further light on the central role of RFX1 down-regulation in the epigenetic de-repression of auto-immune genes in SLE.
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影响因子：
5.2
作者：
Ren, Caiping;Zhao, Ming;Zhang, Hongbo
通讯作者：
Zhang, Hongbo
影响因子：
4
作者：
Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
64.8
作者：
Nielsen, SJ;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
64.8
作者：
Lachner, M;O'Carroll, N;Jenuwein, T
通讯作者：
Jenuwein, T
影响因子：
--
作者：
RICHARDSON, B;POWERS, D;OROURKE, K
通讯作者：
OROURKE, K