Control of chromatin accessibility for V(D)J recombination by interleukin-7

• Published in: Journal of leukocyte biology Vol. 69; no. 6; pp. 907 - 911
• Main Authors: Huang, Jiaqiang, Muegge, Kathrin
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-06-2001
• Subjects: Acetylation; Chromatin - genetics; Chromatin - ultrastructure; DNA Methylation; DNA Nucleotidyltransferases - metabolism; DNA-Binding Proteins - physiology; Evolution, Molecular; Gene Expression Regulation, Developmental - physiology; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor - drug effects; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor - physiology; Histones - metabolism; Homeodomain Proteins - physiology; Humans; immunoglobulin; Interleukin-7 - physiology; Jak3 protein; Lymphocytes - cytology; lymphoid development; Lymphoid Tissue - cytology; Nuclear Proteins; Protein Binding; Protein Processing, Post-Translational; Rag protein; Rag‐1/Rag‐2; Recombination, Genetic - physiology; Retroelements - genetics; Signal Transduction - drug effects; Signal Transduction - physiology; TCR‐γ locus; transposon; VDJ Recombinases
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.69.6.907

IL‐7 is a key factor for lymphoid development, and it contributes to V(D)J recombination at multiple loci in immune‐receptor genes. IL‐7 signal transduction, involving γc and Jak3, is required for successful recombination at the TCR‐γ locus. IL‐7 signaling controls the initiation phase of V(D)J recombination by controlling access of the V(D)J recombinase to the locus. In the absence of IL‐7, the TCR‐γ locus is methylated and packaged in a repressed form of chromatin consisting of hypoacetylated histones. IL‐7 signaling likely increases the acetylation state of the nucleosomal core histones resulting in an “open” form of chromatin. This opening leads to a higher accessibility for the transcription machinery and increased accessibility of the Rag heterodimer that performs the cleavage of DNA.