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

Gang Wei, Lai Wei, Jinfang Zhu, Chongzhi Zang, Jane Hu-Li, Zhengju Yao, Kairong Cui, Yuka Kanno, Tae Young Roh, Wendy T. Watford, Dustin E. Schones, Weiqun Peng, Hong wei Sun, William E. Paul, John J. O'Shea, Keji Zhao

Research output: Contribution to journalArticlepeer-review

951 Scopus citations

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-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.

Original languageEnglish
Pages (from-to)155-167
Number of pages13
JournalImmunity
Volume30
Issue number1
DOIs
StatePublished - 16 Jan 2009

Bibliographical note

Funding Information:
We thank W. Leonard for critical reading of the manuscript and J. Simone for technical help with cell sorting. The gene-expression analysis with the Affymetrix microarrays was performed by the Gene Expression Core Facilities of National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). This research was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases (NIAID), NHLBI, and NIAMS.

Keywords

  • MOLIMMUNO
  • SYSBIO

Fingerprint

Dive into the research topics of 'Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T Cells'. Together they form a unique fingerprint.

Cite this