Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene
Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene
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DOI：
10.1016/s1074-7613(02)00314-x
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发表时间：
2002-05-01
期刊：
影响因子：
32.4
通讯作者：
Rao, A
中科院分区：
文献类型：
--
作者：
Lee, DU;Agarwal, S;Rao, A
CpG甲基化与基因沉默的关系已经很好地建立，但DNA去甲基化在细胞分化过程中对基因表达的贡献仍然不清楚。我们发现，IL-4基因座在T辅助细胞分化过程中经历了一系列复杂的甲基化和去甲基化步骤。iL-4基因座的5'区域在初始T细胞中被高甲基化，并且在Th 2细胞中特异性地被去甲基化，而3'端的高度保守的DNA酶1超敏感区域显示匡威的行为，在初始T细胞中被低甲基化，并且在Th 1分化期间被甲基化。5'去甲基化不是染色质重塑或IL-4基因的初级转录所必需的，但与分化的Th 2细胞对IL-4转录物的有效、高水平诱导密切相关。
The relation of CpG methylation to gene silencing is well established, but the contribution of DNA demethylation to gene expression during cell differentiation remains unclear. We show that the IL-4 locus undergoes a complex series of methylation and demethylation steps during T helper cell differentiation. The 5' region of the iL-4 locus is hypermethylated in naive T cells and becomes specifically demethylated in Th2 cells, whereas a highly conserved DNase 1-hypersensitive region at the 3' end shows the converse behavior, being hypomethylated in naive T cells and becoming methylated during Th1 differentiation. 5' demethylation is not required for chromatin remodeling or primary transcription of the IL-4 gene but is strongly associated with efficient, high-level induction of IL-4 transcripts by differentiated Th2 cells.