GLOBAL MAPPING OF H3K4ME3 AND H3K27ME3 REVEALS SPECIFICITY AND PLASTICITY IN LINEAGE FATE DETERMINATION OF DIFFERENTIATING CD4(+) T CELLS
- GLOBAL MAPPING OF H3K4ME3 AND H3K27ME3 REVEALS SPECIFICITY AND PLASTICITY IN LINEAGE FATE DETERMINATION OF DIFFERENTIATING CD4(+) T CELLS
- Wei, G; Wei, L; Zhu, JF; Zang, CZ; Hu-Li, J; Yao, ZJ; Cui, KR; Kanno, Y; Roh, TY; Watford, WT; Schones, DE; Peng, WQ; Sun, HW; Paul, WE; O'Shea, JJ; Zhao, KJ
- Date Issued
- CELL PRESS
- 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.
- Article Type
- IMMUNITY, vol. 30, no. 1, page. 155 - 167, 2009-01
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