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Cutting Edge |
Loci Accompany Th1/Th2 Differentiation
* Section of Immunobiology, Yale University School of Medicine, and
Howard Hughes Medical Institute, New Haven, CT 06520
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-
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-). In this model, GATA3 and Tbet serve as
transcriptional maintenance factors, which keep the locus accessible to
the transcriptional machinery.
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A. Morinobu, Y. Kanno, and J. J. O'Shea Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression J. Biol. Chem., September 24, 2004; 279(39): 40640 - 40646. [Abstract] [Full Text] [PDF]
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S. Yano, P. Ghosh, H. Kusaba, M. Buchholz, and D. L. Longo Effect of Promoter Methylation on the Regulation of IFN-{gamma} Gene During In Vitro Differentiation of Human Peripheral Blood T Cells into a Th2 Population J. Immunol., September 1, 2003; 171(5): 2510 - 2516. [Abstract] [Full Text] [PDF]
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