Control of chromatin accessibility for V(D)J recombination by interleukin-7.
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 gamma(c) and Jak3, is required for successful recombination at the TCR-gamma 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-gamma 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.
Huang
J
J
Laboratory of Molecular Immuneregulation, SAIC-FCRDC, National Cancer Institute, Frederick, Maryland, USA.
Muegge
K
K
D000107:Acetylation; D002843:Chromatin / Q000235:genetics* / Q000648:ultrastructure; D019175:DNA Methylation; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000187:drug effects / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology; D008221:Lymphoid Tissue / Q000166:cytology; D009687:Nuclear Proteins; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011995:Recombination, Genetic / Q000502:physiology*; D018626:Retroelements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D045567:VDJ Recombinases
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D015851:Interleukin-7; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D018626:Retroelements; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases