Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation.
Peripheral T cell differentiation is accompanied by chromatin changes at the signature cytokine loci. Using chromatin immunoprecipitation we demonstrate that profound increases in histone acetylation occur at the IFN-gamma and IL-4 loci during Th1/Th2 differentiation. These changes in histone acetylation status are locus and lineage specific, and are maintained by the transcription factors Tbet and GATA3 in a STAT-dependent manner. Our results suggest a model of cytokine locus activation in which TCR signals initiate chromatin remodeling and locus opening in a cytokine-independent fashion. Subsequently, cytokine signaling reinforces polarization by expanding and maintaining the accessible state at the relevant cytokine locus (IL-4 or IFN-gamma). In this model, GATA3 and Tbet serve as transcriptional maintenance factors, which keep the locus accessible to the transcriptional machinery.
Fields
Patrick E
PE
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Kim
Sean T
ST
Flavell
Richard A
RA
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005819:Genetic Markers / Q000276:immunology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
D005819:Genetic Markers; D006657:Histones; D015847:Interleukin-4; D007371:Interferon-gamma