Cutting edge: histone acetylation and recombination at the TCR gamma locus follows IL-7 induction.
IL-7 signaling is required for V(D)J recombination at the TCRgamma 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-7Ralpha(-/-) thymocytes in comparison with RAG(-/-) thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7Ralpha(-/-) and IL-7(-/-)RAG(-/-) thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCRgamma 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 TCRgamma locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCRgamma locus.
Huang
J
J
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702, USA.
Durum
S K
SK
Muegge
K
K
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D005333:Fetus; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D005819:Genetic Markers / Q000276:immunology; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D005819:Genetic Markers; D006657:Histones; D018398:Homeodomain Proteins; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7; C064658:RAG-1 protein