Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor

Immunity. 1999 Aug;11(2):213-23. doi: 10.1016/s1074-7613(00)80096-5.

Abstract

IL-7 receptor (IL-7R) plays critical roles in lymphocyte development by promoting survival and proliferation and by inducing V(D)J recombination in TCR and Ig loci. Here, we demonstrate that IL-7R-activated Stat5 binds to consensus motifs in the 5' regions of Jgamma segments and induces germline transcripts. We also show that a constitutively active form of Stat5 restores V-J recombination of TCRgamma genes and partially rescues T cell development from IL-7R(-/-) T cell precursors, especially in favor of gammadelta T cells. Therefore, this study reveals a potential role of Stat5 in T cell development and also implies that IL-7R may control the accessibility of the TCRgamma locus through Stat5-induced germline transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromosome Mapping*
  • DNA-Binding Proteins / physiology*
  • Hematopoietic Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Milk Proteins*
  • Promoter Regions, Genetic
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Interleukin-7 / physiology*
  • Recombination, Genetic
  • STAT5 Transcription Factor
  • T-Lymphocytes / physiology
  • Trans-Activators / physiology*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • Milk Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-7
  • STAT5 Transcription Factor
  • Trans-Activators