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.
Bertolino
Eric
E
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Reddy
Karen
K
Medina
Kay L
KL
Parganas
Evan
E
Ihle
James
J
Singh
Harinder
H
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007135:Immunoglobulin Variable Region; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D015851:Interleukin-7 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008894:Milk Proteins / Q000378:metabolism*; D050811:Octamer Transcription Factor-1; D009841:Oligonucleotides / Q000737:chemistry; D051757:PAX5 Transcription Factor; D063151:Polycomb Repressive Complex 2; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015851:Interleukin-7; D008894:Milk Proteins; D050811:Octamer Transcription Factor-1; D009841:Oligonucleotides; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C494166:Pou2f1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2