Accessibility control of TCR Vγ region by STAT5.
Accessibility control of TCR Vγ region by STAT5.
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DOI：
10.1093/intimm/dxq054
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发表时间：
2010-08
影响因子：
4.4
通讯作者：
S. Tani-ichi;Hai‐Chon Lee;S. Ye;K. Ikuta
中科院分区：
文献类型：
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作者：
S. Tani-ichi;Hai‐Chon Lee;S. Ye;K. Ikuta
IL-7 R和信号转导子和转录激活子（STAT）5的信号通过诱导TCR γ基因座中的V-J重组在γ δ T细胞发育中起重要作用。以前，我们已经表明，STAT 5结合到Jgamma启动子和控制染色质的可及性通过组蛋白乙酰化。然而，关于IL-7 R对Vgamma区的调控机制知之甚少。为了阐明STAT 5的调控，我们首先分析了原代胸腺细胞中V γ区的染色质状态。在Rag 2（-/-）胸腺细胞中，组蛋白H3乙酰化水平在Vgamma 5、HsA元件和Vgamma 2处较高，但在IL-7 R α链（IL-7 R α）缺陷的早期胸腺细胞中较低，表明IL-7 R信号传导控制Vgamma区域的可及性。此外，高水平的组蛋白H3乙酰化和生殖细胞系转录诱导Vgamma 5和HsA细胞因子和STAT 5在依赖精氨酸的Ba/F3和其他造血细胞系。重要的是，细胞因子信号增加了Vgamma 5基因的染色质可及性。此外，STAT 5没有被募集到Vgamma 5启动子的内源性染色质中的非典型STAT结合基序，而STAT 5结合到HsA元件中的共有基序。根据该结果，通过报告基因测定，STAT 5不直接激活V γ 5启动子。这些结果表明，虽然STAT 5直接结合HsA元件并诱导其组蛋白乙酰化，但STAT 5间接激活Vgamma 5启动子。因此，这项研究暗示了STAT 5在Vgamma区域的可及性控制中的潜在作用，特别是在Vgamma 5和HsA。
The signal of the IL-7R and signal transducers and activators of transcription (STAT) 5 plays an essential role in gammadelta T-cell development by inducing V-J recombination in the TCRgamma locus. Previously, we have shown that STAT5 binds to the Jgamma promoters and controls chromatin accessibility by histone acetylation. However, little is known on control mechanism of Vgamma region by the IL-7R. To elucidate the regulation by STAT5, we first analyzed the chromatin status of Vgamma region in primary thymocytes. The levels of histone H3 acetylation are high at Vgamma5, HsA element and Vgamma2 in Rag2(-/-) thymocytes but low in IL-7R alpha-chain (IL-7Ralpha)-deficient early thymocytes, suggesting that IL-7R signaling controls the accessibility of the Vgamma region. In addition, high levels of histone H3 acetylation and germ line transcription were induced at Vgamma5 and HsA by cytokine and STAT5 in cytokine-dependent Ba/F3 and other hematopoietic cell lines. Importantly, the chromatin accessibility of Vgamma5 gene is increased by cytokine signal. Furthermore, STAT5 was not recruited to a non-canonical STAT-binding motif in the endogenous chromatin of the Vgamma5 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 Vgamma5 promoter by reporter assay. These results suggested that while STAT5 directly binds to HsA element and induces its histone acetylation, STAT5 indirectly activates the Vgamma5 promoter. Thus, this study implies a potential role of STAT5 in accessibility control of Vgamma region, especially at Vgamma5 and HsA.