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The Journal of Immunology, 2001, 167: 6073-6077.
Copyright © 2001 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Histone Acetylation and Recombination at the TCR{gamma} Locus Follows IL-7 Induction

Jiaqiang Huang*, Scott K. Durum* and Kathrin Muegge1,*,{dagger}

* Laboratory of Molecular Immunoregulation and {dagger} Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702

IL-7 signaling is required for V(D)J recombination at the TCR{gamma} locus. We have recently reported that IL-7 controls chromatin accessibility for RAG-mediated cleavage. Inhibition of histone deacetylase substituted for the IL-7 signal, indicating a role for histone acetylation in altering chromatin accessibility. We found a greatly reduced histone 3 and histone 4 acetylation level in IL-7R{alpha}-/- thymocytes in comparison with RAG-/- thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7R{alpha}-/- and IL-7-/-RAG-/- thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCR{gamma} constant region in cultured thymocytes from IL-7-/-RAG-/- mice. This induction correlated with increased histone acetylation at the J-promoter and C-enhancer regulatory elements at the TCR{gamma} locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCR{gamma} locus.




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