Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Acetylation
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Chromatin / genetics*
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Chromatin / ultrastructure
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DNA Methylation
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DNA Nucleotidyltransferases / metabolism*
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DNA-Binding Proteins / physiology
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Evolution, Molecular
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Gene Expression Regulation, Developmental / physiology*
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Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / drug effects
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Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / physiology*
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Histones / metabolism
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Homeodomain Proteins / physiology
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Humans
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Interleukin-7 / physiology*
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Lymphocytes / cytology
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Lymphoid Tissue / cytology
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Nuclear Proteins
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Protein Binding
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Protein Processing, Post-Translational
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Recombination, Genetic / physiology*
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Retroelements / genetics
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Signal Transduction / drug effects
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Signal Transduction / physiology
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VDJ Recombinases
Substances
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Chromatin
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DNA-Binding Proteins
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Histones
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Homeodomain Proteins
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Interleukin-7
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Nuclear Proteins
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RAG2 protein, human
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Retroelements
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V(D)J recombination activating protein 2
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RAG-1 protein
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DNA Nucleotidyltransferases
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VDJ Recombinases