Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation.
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.
Agarwal
S
S
Department of Pathology, Harvard Medical School, Center for Blood Research, Boston, Massachusetts 02115, USA. arao@cbr.med.harvard.edu
Rao
A
A
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry* / Q000502:physiology*; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000166:cytology
D002843:Chromatin; D018793:Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma