Th cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes

Orly Avni, Dong Lee, Fernando Macian, Susanne J. Szabo, Laurie H. Glimcher, Anjana Rao

Research output: Contribution to journalArticle

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Abstract

Naïve T cells differentiate into effector cells upon stimulation with antigen, a process that is accompanied by changes in the chromatin structure of effector cytokine genes. Using histone acetylation to evaluate these changes, we showed that T cell receptor (TCR) stimulation results in early activation of the genes encoding both interleukin 4 and interferon-γ. We found that continued culture in the presence of polarizing cytokines established a selective pattern of histone acetylation on both cytokine genes; this correlated with restricted access of the transcription factor NFATI to these gene regulatory regions as well as mutually exclusive gene expression by the differentiated T cells. Our data point to a biphasic process in which cytokine-driven signaling pathways maintain and reinforce chromatin structural changes initiated by the TCR. This process ensures that cytokine genes remain accessible to the relevant transcription factors and promotes functional cooperation of the inducible transcription factor NFAT with lineage-specific transcription factors such as GATA-3 and T-bet.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalNature Immunology
Volume3
Issue number7
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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