PU.1 can participate in an active enhancer complex without its transcriptional activation domain.
PU.1 can participate in an active enhancer complex without its transcriptional activation domain.
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DOI：
10.1073/pnas.94.1.127
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发表时间：
1997-01
影响因子：
11.1
通讯作者：
J. Pongubala;M. Atchison
中科院分区：
文献类型：
--
作者：
J. Pongubala;M. Atchison
转录因子 PU.1 对于多种造血谱系的发育是必需的，并有助于免疫球蛋白 kappa 3' 增强子的活性。多种蛋白质与 3' 增强子结合（PU.1、PIP、ATF1、CREM、c-Fos、c-Jun 和 E2A），但 3' 增强子活性的机制及其活性所需的蛋白质目前尚不清楚。我们在此表明 PU.1 与其他转录因子一起参与形成具有 3'-增强子 DNA 序列的高阶复合物。每种蛋白质对于该复合物的形成都是必需的。单独而言，与 3' 增强子结合的转录因子不会明显刺激 3' 增强子通常沉默的细胞类型中的转录 (NIH 3T3)。然而，多种转录因子（PU.1、PIP、c-Fos 和 c-Jun）的混合物可以极大地激活增强子。 PU.1 对于最大增强子活性是必需的，但缺乏转录激活结构域的 PU.1 突变体在刺激增强子活性方面几乎与野生型 PU.1 蛋白一样有效。 PU.1 显然可以通过在与其他转录因子相互作用中发挥结构作用来激活转录。
The transcription factor PU.1 is necessary for the development of multiple hematopoietic lineages and contributes to the activity of the immunoglobulin kappa 3' enhancer. A variety of proteins bind to the 3' enhancer (PU.1, PIP, ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3'-enhancer activity and the proteins necessary for its activity are presently unclear. We show here that PU.1 participates with other transcription factors in forming a higher-order complex with 3'-enhancer DNA sequences. Each protein is necessary for formation of this complex. Individually, transcription factors that bind to the 3' enhancer do not appreciably stimulate transcription in a cell type in which the 3' enhancer is normally silent (NIH 3T3). However, mixture of multiple transcription factors (PU.1, PIP, c-Fos, and c-Jun) can greatly activate the enhancer. PU.1 is necessary for maximal enhancer activity, but mutants of PU.1 that lack the transcriptional activation domain are nearly as efficient at stimulating enhancer activity as the wild-type PU.1 protein. PU.1 apparently can activate transcription by playing an architectural role in interactions with other transcription factors.