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Cutting edge: Histone acetylation and recombination at the TCR gamma locus follows IL-7 induction

  1. Author:
    Huang, J. Q.
    Durum, S. K.
    Muegge, K.

  2. Author Address

    NCI, Mol Immunoregulat Lab, Bldg 469, Room 243, Ft Detrick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. NCI, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. Muegge K NCI, Mol Immunoregulat Lab, Bldg 469, Room 243, Ft Detrick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Journal of Immunology
    1. 167
    2. 11
    3. Pages: 6073-6077
  4. Type of Article: Article
  1. Abstract:

    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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