Chromatin remodeling at the Th2 cytokine gene loci in human type 2 helper T cells
Chromatin remodeling at the Th2 cytokine gene loci in human type 2 helper T cells
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DOI：
10.1016/j.molimm.2006.11.004
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Kaneko, Takaaki;Hosokawa, Hiroyuki;Nakayama, Toshinori
小鼠初始CD4 T细胞向2型辅助细胞（Th2）的分化伴随着与IL-4、IL-13和IL-5基因相关的核小体的染色质重塑。然而，对于这些Th2细胞因子基因位点的染色质重塑是如何在人类Th2细胞中发生的，我们知之甚少。我们在此建立了一个体外培养系统，在此系统中Th1和Th2细胞都能从人外周血初始CD4 T细胞中有效分化出来。该系统使我们能够分别研究人类Th2和Th1细胞中Th2细胞因子基因位点和ifn - γ位点的染色质状态。在典型个体中，在发育中的Th2细胞中，在整个Th2细胞因子基因位点上诱导了组蛋白H3赖氨酸9的超乙酰化和组蛋白H3赖氨酸4的超甲基化所表明的染色质重塑。在20名健康志愿者制备的Th1和Th2细胞中，我们更精确地评估了Th2细胞因子基因位点（IL-5外显子3、IL-5启动子、IL-5/RAD50基因间区、RAD50启动子、CGRE、CNS1、IL-13启动子、IL-4启动子和V-A增强子区域）和IFN γ位点上组蛋白H3赖氨酸4的甲基化状态。大多数Th2细胞因子基因位点均可诱导Th2细胞特异性染色质重塑。在诱导染色质重塑的同时，GATA3 mRNA在发育中的Th2细胞中优先表达，而T-bet、HLX和ROG mRNA在发育中的Th1细胞中选择性表达。(c) 2006 Elsevier Ltd.版权所有。
The differentiation of mouse naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling at the nucleosomes associated with the IL-4, IL-13 and IL-5 genes. However, little is known about how chromatin remodeling of these Th2 cytokine gene loci occurs in human Th2 cells. We herein established an in vitro culture system in which both Th1 and Th2 cells are efficiently differentiated from human peripheral blood naive CD4 T cells. This system allowed us to investigate the chromatin status at the Th2 cytokine gene loci and the IFN-gamma locus in human Th2 and Th1 cells, respectively. In typical individuals, the chromatin remodeling indicated by the induction of hyper-acetylation of histone H3 lysine 9 and hyper-methylation of histone H3 lysine 4 was induced at the whole Th2 cytokine gene loci in developing Th2 cells. We more precisely assessed the methylation status of histone H3 lysine 4 at the Th2 cytokine gene loci (IL-5 exon 3, IL-5 promoter, IL-5/RAD50 intergenic region, RAD50 promoter, CGRE, CNS1, IL-13 promoter, IL-4 promoter, and V-A enhancer regions) and the IFN gamma locus in developing Th1 and Th2 cells prepared from 20 healthy volunteers. Th2-cell specific chromatin remodeling was induced at most of the Th2 cytokine gene loci. In parallel with the induction of chromatin remodeling, GATA3 mRNA was preferentially expressed in developing Th2 cells, whereas T-bet, HLX and ROG mRNA was selectively expressed in developing Th1 cells. (c) 2006 Elsevier Ltd. All rights reserved.