Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor.
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.
Ye
S K
SK
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Maki
K
K
Kitamura
T
T
Sunaga
S
S
Akashi
K
K
Domen
J
J
Weissman
I L
IL
Honjo
T
T
Ikuta
K
K
D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008894:Milk Proteins; D011401:Promoter Regions, Genetic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D011995:Recombination, Genetic; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D015534:Trans-Activators