| Abstract
| - The signal of the IL-7R and signal transducers and activators of transcription (STAT) 5 plays an essential role in γδ T-cell development by inducing V-J recombination in the TCRγ locus. Previously, we have shown that STAT5 binds to the Jγ promoters and controls chromatin accessibility by histone acetylation. However, little is known on control mechanism of Vγ region by the IL-7R. To elucidate the regulation by STAT5, we first analyzed the chromatin status of Vγ region in primary thymocytes. The levels of histone H3 acetylation are high at Vγ5, HsA element and Vγ2 in Rag2−/− thymocytes but low in IL-7R α-chain (IL-7Rα)-deficient early thymocytes, suggesting that IL-7R signaling controls the accessibility of the Vγ region. In addition, high levels of histone H3 acetylation and germ line transcription were induced at Vγ5 and HsA by cytokine and STAT5 in cytokine-dependent Ba/F3 and other hematopoietic cell lines. Importantly, the chromatin accessibility of Vγ5 gene is increased by cytokine signal. Furthermore, STAT5 was not recruited to a non-canonical STAT-binding motif in the endogenous chromatin of the Vγ5 promoter by cytokine stimulation, while STAT5 binds to a consensus motif in the HsA element. In accordance with this result, STAT5 does not directly activate the Vγ5 promoter by reporter assay. These results suggested that while STAT5 directly binds to HsA element and induces its histone acetylation, STAT5 indirectly activates the Vγ5 promoter. Thus, this study implies a potential role of STAT5 in accessibility control of Vγ region, especially at Vγ5 and HsA.
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