Accessibility control of TCR V-gamma region by STAT5

作者：Tani ichi Shizue; Lee Hai Chon; Ye Sang Kyu; Ikuta Koichi^*

来源：International Immunology, 2010, 22(8): 693-703.

DOI：10.1093/intimm/dxq054

• chromatin
• IL-7
• gamma delta T cell
• transcription factor
• V(D)J recombination

The signal of the IL-7R and signal transducers and activators of transcription (STAT) 5 plays an essential role in gamma delta T-cell development by inducing V-J recombination in the TCR gamma locus. Previously, we have shown that STAT5 binds to the J gamma promoters and controls chromatin accessibility by histone acetylation. However, little is known on control mechanism of V gamma region by the IL-7R. To elucidate the regulation by STAT5, we first analyzed the chromatin status of V gamma region in primary thymocytes. The levels of histone H3 acetylation are high at V gamma 5, HsA element and V gamma 2 in Rag2(-/-) thymocytes but low in IL-7R alpha-chain (IL-7R alpha)-deficient early thymocytes, suggesting that IL-7R signaling controls the accessibility of the V gamma region. In addition, high levels of histone H3 acetylation and germ line transcription were induced at V gamma 5 and HsA by cytokine and STAT5 in cytokine-dependent Ba/F3 and other hematopoietic cell lines. Importantly, the chromatin accessibility of V gamma 5 gene is increased by cytokine signal. Furthermore, STAT5 was not recruited to a non-canonical STAT-binding motif in the endogenous chromatin of the V gamma 5 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 V gamma 5 promoter by reporter assay. These results suggested that while STAT5 directly binds to HsA element and induces its histone acetylation, STAT5 indirectly activates the V gamma 5 promoter. Thus, this study implies a potential role of STAT5 in accessibility control of V gamma region, especially at V gamma 5 and HsA.

• 出版日期2010-8