Nature Immunology
6, 836 - 843 (2005)
Published online: 17 July 2005; | doi:10.1038/ni1226
Regulation of interleukin 7−dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5Eric Bertolino1, Karen Reddy1, 2, Kay L Medina1, Evan Parganas3, James Ihle3
& Harinder Singh1, 21
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA. 2
Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA. 3
Department of Biochemistry, Howard Hughes Medical Institute St. Jude's Children's Research Hospital, Memphis, Tennessee 38105, USA.
Correspondence should be addressed to Harinder Singh hsingh@uchicago.edu Rearrangement of immunoglobulin heavy-chain variable (VH) 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 VH 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 VH gene segments. STAT5 associated with VH 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 VH recombination in relation to the transcription factor Pax5 and histone methyltransferase Ezh2.
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