Epigenetic regulation of beta2-adrenergic receptor expression in T(H)1 and T(H)2 cells.
Epigenetic regulation of beta2-adrenergic receptor expression in T(H)1 and T(H)2 cells.
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DOI：
10.1016/j.bbi.2010.10.019
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发表时间：
2011-03
影响因子：
15.1
通讯作者：
Sanders, Virginia M.
中科院分区：
文献类型：
--
作者：
McAlees, Jaclyn W.;Smith, Laura T.;Erbe, Robert S.;Jarjoura, David;Ponzio, Nicholas M.;Sanders, Virginia M.
我们以前发现，小鼠幼稚CD 4 + T细胞和TH 1细胞克隆表达β 2-肾上腺素能受体（β2AR），而TH 2细胞克隆不表达。我们在此报道，在TH 1驱动条件下分化1-5天的幼稚CD 4 + T细胞增加β2AR基因表达，而在TH 2驱动条件下培养的细胞降低β2AR基因表达。染色质免疫沉淀显示，TH 1细胞中β 2 AR基因表达的增加是由组蛋白3（H3）和H4乙酰化的增加以及组蛋白3赖氨酸4（H3 K4）甲基化的增加介导的。相反，TH 2细胞中β2AR基因表达的降低是由H3和H4乙酰化的降低和H3 K4甲基化的降低以及H3 K9和H3 K27甲基化的增加介导的。组蛋白的变化，可以检测到早在3天的分化条件。基因组亚硫酸氢盐测序显示，与初始和TH 1细胞相比，TH 2细胞中β2AR基因启动子内甲基化CpG二核苷酸的水平增加。总的来说，这些结果表明，表观遗传机制分别介导TH 1和TH 2驱动细胞中β2AR基因表达的维持和抑制，提供了一种潜在的机制，通过该机制，β2AR表达水平可能在免疫细胞和其他细胞类型中被调节，其中表达谱可能在疾病过程中发生变化。
We showed previously that murine naive CD4+ T cells and TH1 cell clones express the beta2-adrenergic receptor (β2AR), while TH2 cell clones do not. We report here that naive CD4+ T cells that differentiated for 1-5 days under TH1 driving conditions increased β2AR gene expression, while cells cultured under TH2 driving conditions decrease β2AR gene expression. Chromatin immunoprecipitation revealed that the increase in β2AR gene expression in TH1 cells is mediated by an increase in histone 3 (H3) and H4 acetylation, as well as an increase in histone 3 lysine 4 (H3K4) methylation. Conversely, the decrease in β2AR gene expression in TH2 cells is mediated by a decrease in H3 and H4 acetylation and a decrease in H3K4 methylation, as well as an increase H3K9 and H3K27 methylation. The histone changes could be detected as early as 3 days of differentiating conditions. Genomic bisulfite sequencing showed that the level of methylated CpG dinucleotides within the promoter of the β2AR gene was increased in TH2 cells as compared to naive and TH1 cells. Collectively, these results suggest that epigenetic mechanisms mediate maintenance and repression, respectively, of the β2AR gene expression in TH1- and TH2-driven cells, providing a potential mechanism by which the level of β2AR expression might be modulated pharmacologically within immune cells and other cell types in which the expression profile may change during a disease process.
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