Cutting Edge: Changes in Histone Acetylation at the IL-4 and IFN- Loci Accompany Th1/Th2 Differentiation

Yale University, New Haven, Connecticut, United States
The Journal of Immunology (Impact Factor: 4.92). 08/2002; 169(2):647-50. DOI: 10.4049/jimmunol.169.2.647
Source: PubMed


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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    • "The hypermethylation of the first exon is correlated with promoter hypermethylation resulting in transcriptional silencing. The early response is marked by increases in IL-4 expression because the GATA-3 transcriptional factor binding sites within the first intron of the gene loses CpG methylation and the IL 4 locus gains H3K9 acetylation and trimethylation of H3K4 [8]. Th2 polarization is associated with loss of interferon (IFN)-g expression, which is thought to be mediated by methylation of specific CpGs in its promoter region [9, 10]. "
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