[PDF][PDF] Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells

G Wei, L Wei, J Zhu, C Zang, J Hu-Li, Z Yao, K Cui… - Immunity, 2009 - cell.com
G Wei, L Wei, J Zhu, C Zang, J Hu-Li, Z Yao, K Cui, Y Kanno, TY Roh, WT Watford…
Immunity, 2009cell.com
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 …
Summary
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, Il4, and Il17) 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-γ 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.
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