Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5

Eric Bertolino, Karen Reddy, Kay L. Medina, Evan Parganas, James Ihle, Harinder Singh

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)836-843
Number of pages8
JournalNature immunology
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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