title: Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells.
abstract: 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-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.
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zang
authors.forename: Jane
authors.initials: J
authors.lastname: Hu-Li
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Dustin E
authors.initials: DE
authors.lastname: Schones
authors.forename: Weiqun
authors.initials: W
authors.lastname: Peng
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D006657:Histones / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases; D051379:Mice; D008810:Mice, Inbred C57BL; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000276:immunology; D046188:Protein Modification, Translational; D056485:Retinoblastoma-Binding Protein 2; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse; D056485:Retinoblastoma-Binding Protein 2; C523761:Kdm6b protein, mouse; D010089:Oxidoreductases, N-Demethylating