Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5.
Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells. However, the genetic evidence for this recombination pathway has been challenged. Furthermore, no molecular components that directly control V(H) gene rearrangement have been elucidated. Using mice deficient in the ... interleukin 7-activated transcription factor STAT5, we demonstrate here that STAT5 regulated germline transcription, histone acetylation and DNA recombination of distal V(H) gene segments. STAT5 associated with V(H) gene segments in vivo and was recruited as a coactivator with the transcription factor Oct-1. STAT5 did not affect the nuclear repositioning or compaction of the immunoglobulin heavy-chain locus. Therefore, STAT5 functions at a distinct step in regulating distal V(H) recombination in relation to the transcription factor Pax5 and histone methyltransferase Ezh2.
Mesh Terms:
Animals, B-Cell-Specific Activator Protein, B-Lymphocytes, Cell Nucleus, Chromatin, Chromatin Immunoprecipitation, DNA-Binding Proteins, Gene Rearrangement, Histone-Lysine N-Methyltransferase, Histones, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Immunoprecipitation, In Situ Hybridization, Fluorescence, Interleukin-7, Mice, Mice, Transgenic, Microscopy, Fluorescence, Milk Proteins, Octamer Transcription Factor-1, Oligonucleotides, Polymerase Chain Reaction, Promoter Regions, Genetic, Proteins, RNA, Messenger, Recombination, Genetic, Reverse Transcriptase Polymerase Chain Reaction, STAT5 Transcription Factor, Stem Cells, Trans-Activators, Transcription Factors, Transcription, Genetic
Animals, B-Cell-Specific Activator Protein, B-Lymphocytes, Cell Nucleus, Chromatin, Chromatin Immunoprecipitation, DNA-Binding Proteins, Gene Rearrangement, Histone-Lysine N-Methyltransferase, Histones, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Immunoprecipitation, In Situ Hybridization, Fluorescence, Interleukin-7, Mice, Mice, Transgenic, Microscopy, Fluorescence, Milk Proteins, Octamer Transcription Factor-1, Oligonucleotides, Polymerase Chain Reaction, Promoter Regions, Genetic, Proteins, RNA, Messenger, Recombination, Genetic, Reverse Transcriptase Polymerase Chain Reaction, STAT5 Transcription Factor, Stem Cells, Trans-Activators, Transcription Factors, Transcription, Genetic
Nat. Immunol.
Date: Aug. 01, 2005
PubMed ID: 16025120
View in: Pubmed Google Scholar
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