Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T Cells

被引:893
作者
Wei, Gang [2 ]
Wei, Lai [1 ]
Zhu, Jinfang
Zang, Chongzhi [4 ]
Hu-Li, Jane
Yao, Zhengju [1 ]
Cui, Kairong [2 ]
Kanno, Yuka [1 ]
Roh, Tae-Young [2 ]
Watford, Wendy T. [1 ]
Schones, Dustin E. [2 ]
Peng, Weiqun [4 ]
Sun, Hong-wei [3 ]
Paul, William E.
O'Shea, John J. [1 ]
Zhao, Keji [2 ]
机构
[1] NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA
[2] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA
[3] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA
[4] George Washington Univ, Dept Phys, Washington, DC 20052 USA
关键词
EMBRYONIC STEM-CELLS; HUMAN GENOME; GENE-EXPRESSION; TGF-BETA; TRANSCRIPTION FACTORS; FOXP3; EXPRESSION; HELPER TYPE-1; T(H)17 CELLS; TH17; CELLS; TH2;
D O I
10.1016/j.immuni.2008.12.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Multipotential naive CD4(+) T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4(+) T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naive, Th1, Th2, Th17, iTreg, and natural Treg (nTreg) cells. We found that although modifications of signature-cytokine genes (Ifng, II4, and II17) partially conform to the expectation of lineage commitment, genes encoding transcription factors like Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and interferon-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4(+) T helper cell differentiation.
引用
收藏
页码:155 / 167
页数:13
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