Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells
Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells
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DOI：
10.1074/jbc.m405989200
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发表时间：
2004-09-17
影响因子：
4.8
通讯作者：
Nakayama, T
中科院分区：
文献类型：
--
作者：
Yamashita, M;Shinnakasu, R;Nakayama, T
白细胞介素（IL）-4诱导的STAT 6活化和随后的GATA 3上调对于在Th 2细胞发育过程中诱导Th 2细胞因子基因位点的染色质重塑至关重要。本研究探讨了这些分子在维持记忆性Th 2细胞中的作用。不需要IL-4来维持在体内产生的抗原特异性记忆Th 2细胞中产生Th 2细胞因子的能力。组蛋白H3 K9/14超乙酰化和与IL-4基因位点相关的基因间转录物在IL-4不存在的情况下得以保留，但与IL-13基因相关的转录物部分依赖于IL-4。IL-13和IL-4基因位点的组蛋白H3-K4甲基化在记忆性Th 2细胞中被完全保留，并伴随着Pol II复合物在高度限制性位点的记忆细胞特异性积累。因此，记忆性Th 2细胞通过不依赖于IL-4的活性分子事件在IL-4和IL-13基因座中维持独特的Th 2特异性重塑染色质。
Interleukin (IL)-4-induced STAT6 activation and the subsequent up-regulation of GATA3 are crucial for the induction of chromatin remodeling of the Th2 cytokine gene loci as Th2 cells undergo development. This study probes the role of these molecules in the maintenance of memory Th2 cells. IL-4 was not required to maintain the capability for Th2 cytokine production in in vivo generated antigen-specific memory Th2 cells. Histone H3K9/14 hyperacetylation and intergenic transcripts associated with the IL-4 gene locus were preserved in the absence of IL-4, but those associated with the IL-13 gene were partially IL-4-dependent. Histone H3-K4 methylation of the IL-13 and IL-4 gene loci was fully preserved in memory Th2 cells and accompanied by memory cell-specific accumulation of Pol II complex to highly restricted sites. Thus, memory Th2 cells maintain a unique Th2-specific remodeled chromatin in the IL-4 and IL-13 gene loci by active molecular events that are IL-4-independent.