Regulation of thymocyte survival by transcriptional coactivators.
Regulation of thymocyte survival by transcriptional coactivators.
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DOI：
10.1615/critrevimmunol.v26.i6.10
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发表时间：
2006
影响因子：
1.3
通讯作者：
H. Xie;Zhaofeng Huang;Ruiqing Wang;Zuoming Sun
中科院分区：
文献类型：
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作者：
H. Xie;Zhaofeng Huang;Ruiqing Wang;Zuoming Sun
由于不符合阳性和阴性选择标准，大多数发育中的T细胞被凋亡所消除。因此，发育中的T细胞容易受到凋亡信号的影响。另一方面，也有防止发育中的T细胞过早凋亡的机制。因此，维持生与死之间的良好平衡是成功完成T细胞发育的关键。我们最近的研究表明，转录共激活因子在维持T细胞发育的这种平衡中起着至关重要的作用。转录辅活化子被转录因子招募，通过改变染色质结构来定量调节基因表达。两种转录因子，TCF-1和RoR-Gamma t，需要上调Bcl-xL的水平，这是CD4+CD8+双阳性胸腺细胞的关键生存因子。然而，TCF-1和ROR-γt本身并不足以刺激Bclxl的表达。转录辅活化子β-连环素由TCF-1招募，类固醇受体辅活化子(SRCs)由ROR-Gamma t招募，也是最佳刺激Bcl-xL表达所必需的。因此，转录共激活因子是转录机制的重要组成部分，以调节胸腺细胞的存活，确保T细胞发育的完成。
A majority of the developing T cells are eliminated by apoptosis because they do not meet the positive and negative selection criteria. Developing T cells are thus susceptible to apoptotic signals. On the other hand, there are mechanisms to prevent developing T cells from premature apoptosis. Maintenance of a fine balance between life and death is thus critical for successful completion of T-cell development. Our recent studies demonstrated an essential role of transcriptional coactivators in maintaining such a balance for developing T cells. Transcriptional coactivators are recruited by transcriptional factors to quantitatively regulate gene expression via modifying chromatin structure. Two transcriptional factors, TCF-1 and ROR gamma t, are required to upregulate the levels of Bcl-xL, a critical survival factor for CD4+CD8+ double-positive thymocytes. However, TCF-1 and ROR gamma t by themselves are not sufficient to stimulate Bcl-xL expression. Transcriptional coactivator beta-catenin recruited by TCF-1, and steroid receptor coactivators (SRCs) recruited by ROR gamma t, are also required for optimal stimulation of Bcl-xL expression. Thus, transcriptional coactivators are a substantial component of the transcriptional machinery to regulate thymocye survival, ensuring the completion of T-cell development.