Dynamic changes in histone-methylation 'marks' across the locus encoding interferon-γ during the differentiation of T helper type 2 cells

被引:139
作者
Chang, Shaojing
Aune, Thomas M.
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Div Rheumatol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Immunol & Microbiol, Nashville, TN 37232 USA
关键词
D O I
10.1038/ni1473
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The 'histone-code' hypothesis proposes that cell fate 'decisions' are achieved through the creation of stable epigenetic histone 'marks' at gene loci. Here we explored the formation of marks of repressive methylation of histone 3 at lysine 9 (H3-K9) and of H3-K27 at the locus encoding interferon-gamma (Ifng locus) during the commitment of naive T cells to the T helper type 1 (T(H)1) and T(H)2 lineages. Methylation of H3-K9 across the Ifng locus was rapidly induced in differentiating T(H)1 and T(H)2 cells and was sustained in TH1 cells. In contrast, TH2 differentiation caused loss of methylation of H3-K9 and gain of methylation of H3-K27 by mechanisms dependent on the transcription factors GATA-3 and STAT6. Thus, histone-methylation marks at the Ifng locus are highly dynamic, which may ensure higher-order transcriptional regulation during early lineage commitment.
引用
收藏
页码:723 / 731
页数:9
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