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Science  26 Jul 2002:
Vol. 297, Issue 5581, pp. 481
DOI: 10.1126/science.297.5581.481c

Commitment of CD4+ T cells to the T helper cell 1 (TH1) or TH2 lineage is defined by the transcription of IFNγ and interleukin-4 (IL-4) cytokine genes, respectively. Potentially, this could be specified at the early stages of naïve T cell activation or during the subsequent elaboration of helper cell functions.

Fields et al. and Avini et al. used chromatin immunoprecipitation to obtain information about chromatin conformations at the IL-4 and IFNγ loci during T helper cell differentiation. Acetylation of histone tail domains (representing an open chromatin structure accessible to the transcription machinery) appeared at both loci in response to early signals from the T cell receptor. However, acetylation at each locus was maintained only in the presence of the correct cytokine stimulus. In the case of TH2 signals, signal transducer and activator of transcription-6 (STAT-6) initiated cooperation of the transcription factors GATA-3 and NFAT in stabilizing the IL-4 locus. Fields et al. also observed that STAT-4-dependent TH1 signals induced stabilization of the IFNγ locus via the transcriptional regulator T-bet. This two-tiered regulation of cytokine locus accessibility was mutually exclusive, because chromatin at the nonspecified locus was secured in a state not permissive for gene transcription. — SJS

J. Immunol.169, 647 (2002); Nature Immunol.3, 643 (2002).

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