Article

Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation.

Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
The Journal of Immunology (Impact Factor: 5.36). 08/2002; 169(2):647-50. DOI: 10.4049/jimmunol.169.2.647
Source: PubMed

ABSTRACT 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.

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