Modulation of Chromatin Structure Regulates Cytokine Gene Expression During T Cell Differentiation

Immunity. 1998 Dec;9(6):765-75. doi: 10.1016/s1074-7613(00)80642-1.

Abstract

Differentiating cells undergo programmed alterations in their patterns of gene expression, which are often regulated by structural changes in chromatin. Here we demonstrate that T cell differentiation results in long-range changes in the chromatin structure of effector cytokine genes, which persist in resting Th1 and Th2 cells in the absence of further stimulation. Differentiation of naive T helper cells into mature Th2 cells is associated with chromatin remodeling of the IL-4 and IL-13 genes, whereas differentiation into Th1 cells evokes remodeling of the IFNgamma but not IL-4 or IL-13 genes. IL-4 locus remodeling is accompanied by demethylation and requires both antigen stimulation and STAT6 activation. We propose that chromatin remodeling of cytokine gene loci is functionally associated with productive T cell differentiation and may explain the coordinate regulation of Th2 cytokine genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Chromatin / chemistry*
  • Chromatin / physiology*
  • CpG Islands
  • DNA Methylation
  • Gene Expression Regulation
  • Interferon-gamma / genetics*
  • Interleukin-13 / genetics*
  • Interleukin-4 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Th2 Cells* / cytology

Substances

  • Chromatin
  • Interleukin-13
  • Interleukin-4
  • Interferon-gamma