The IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation.
The IL-7 receptor (IL-7R) plays critical roles in expansion and V(D)J recombination during lymphocyte development. Here we demonstrate that cytokine stimulation rapidly recruits Stat5 and transcriptional coactivators to the Jgamma germline promoter and induces histone acetylation, germline transcription, and accessibility in Ba/F3 cells. We also show that histone acetylation of the TCRgamma locus is significantly reduced in IL-7R-deficient thymocytes and that the introduction of active Stat5 restores the histone acetylation and accessibility of the locus. Furthermore, treatment with histone deacetylase inhibitor recovers the histone acetylation and accessibility in IL-7R-deficient thymocytes. Therefore, these results suggest that Stat5 may recruit the transcriptional coactivators to the Jgamma germline promoter and control the accessibility of the TCRgamma locus by histone acetylation.
Ye
S K
SK
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Agata
Y
Y
Lee
H C
HC
Kurooka
H
H
Kitamura
T
T
Shimizu
A
A
Honjo
T
T
Ikuta
K
K
D000107:Acetylation; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006657:Histones / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology*; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*
D004268:DNA-Binding Proteins; D006657:Histones; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D015534:Trans-Activators