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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The Ets factor Spi-B is a direct critical target of the coactivator OBF-1
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The Ets factor Spi-B is a direct critical target of the coactivator OBF-1

机译：Ets因子Spi-B是共激活剂OBF-1的直接关键目标

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摘要

OBF-1 (Bob.1, OCA-B) is a lymphoid-specific transcriptional coactivator that associates with the transcription factors Oct-1 or Oct-2 on the conserved octamer element present in the promoters of several ubiquitous and lymphoid-specific genes. OBF-1-deficient mice have B cell-intrinsic defects, lack germinal centers, and have severely impaired immune responses to T cell-dependent antigens. Crucial genes that are regulated by OBF-1 and that might explain the observed phenotype of OBF-1 deficiency have remained elusive to date. Here we have generated transgenic mice expressing OBF-1 specifically in T cells and examined these together with mice lacking OBF-1 to discover transcriptional targets of this coactivator. Using microarray analysis, we have identified the Ets transcription factor Spi-B as a direct target gene critically regulated by OBF-1 that can help explain the phenotype of OBF-1-deficient mice. Spi-B has been implicated in signaling pathways downstream of the B cell receptor and is essential for germinal center formation and maintenance. The present findings establish a hierarchy between these two factors and provide a molecular link between OBF-1 and B cell receptor signaling.
机译：OBF-1（Bob.1，OCA-B）是一种淋巴样特异性转录共激活因子，与几种普遍存在的和淋巴样特异性基因的启动子中存在的保守八聚体元件上的转录因子Oct-1或Oct-2相关。缺乏OBF-1的小鼠具有B细胞固有缺陷，缺乏生发中心，并且对T细胞依赖性抗原的免疫反应严重受损。迄今为止，由OBF-1调控并可能解释观察到的OBF-1缺陷表型的关键基因仍然难以捉摸。在这里，我们已经生成了在T细胞中特异性表达OBF-1的转基因小鼠，并与缺乏OBF-1的小鼠一起检查了这些转基因小鼠以发现该共激活因子的转录靶标。使用微阵列分析，我们已经确定Ets转录因子Spi-B是由OBF-1严格调控的直接靶基因，可以帮助解释OBF-1缺陷型小鼠的表型。 Spi-B与B细胞受体下游的信号通路有关，对生发中心的形成和维持至关重要。本研究结果建立了这两个因素之间的层次结构，并提供了OBF-1和B细胞受体信号传导之间的分子联系。

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