Androgen receptor interactions with Oct-1 and Brn-1 are physically and functionally distinct
Androgen receptor interactions with Oct-1 and Brn-1 are physically and functionally distinct
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DOI：
10.1016/s0303-7207(02)00035-7
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发表时间：
2002-04-25
影响因子：
4.1
通讯作者：
Robins, DM
中科院分区：
文献类型：
--
作者：
González, MI;Tovaglieri, A;Robins, DM
POU结构域蛋白与类固醇激素受体积极或消极地相互作用，这取决于这些和靶基因启动子上组装的其他因子的精确阵列。八聚体转录因子1（Oct-1）是一种普遍存在的POU因子，参与了基于油蛋白-DNA相互作用研究的小鼠性限制蛋白（Slp）基因的雄激素诱导。然而，Oct-1在激素反应中的作用的直接证据一直难以获得。脑1（Brn-1）是另一种POU因子，具有更高的组织特异性，在脑中表达，也在肾脏中表达，肾脏是Slp合成的主要部位。我们比较了雄激素受体（AR）与Oct-1和Brn-1的相互作用，以揭示更有可能调节Slp的候选者。在转染中，Oct-1或Brn-1的加入降低了AR激活，而不管增强子中是否存在八聚体样序列，这表明干扰是间接的。然而，当八聚体样元素被改变为一个共识八聚体网站，Brn-1，而不是Oct-1，强烈增强雄激素激活。这与Brn-1在DNA结合测定中对共有八聚体序列的偏好相关。AR与谷胱甘肽-S-转移酶-（GST）融合的Oct-1的直接相互作用是DNA依赖性的，而Brn-1-AR的关联不是。Brn-1和Oct-1嵌合的POU结构域表明，DNA依赖的AR相互作用依赖于POU同源结构域的起源。然而，在全长Brn-1和Oct-1嵌合蛋白的背景下，POU homedomain不足以赋予这些因子在体内的不同行为，而是揭示了Brn-1中N-末端反式激活结构域的重要性。这些结果表明，Oct-1和Brn-1与AR的功能性相互作用是由八聚体结合位点的精确序列以及POU因子与AR和转录机制的其他组分的差异性相互作用决定的。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
POU domain proteins interact positively or negatively with steroid hormone receptors, depending on the precise array of these and other factors assembled on target gene promoters. Octamer transcription factor 1 (Oct-1), a ubiquitous POU factor, is implicated in androgen induction of the mouse sex-limited protein (Slp) gene based oil protein-DNA interaction studies. However, direct evidence for a role of Oct-1 in the hormone response has been difficult to obtain. Brain 1 (Brn-1), another POU factor, is more tissue-specific, expressing in brain and also in kidney, which is a major site of Slp synthesis. We compared the interaction of the androgen receptor (AR) with Oct-1 and Brn-1 to reveal the more likely candidate for regulation of Slp. In transfection, addition of either Oct-1 or Brn-1 reduced AR activation, regardless of the presence of an octamer-like sequence in the enhancer, suggesting interference was indirect. However, when the octamer-like element was changed to a consensus octamer site, Brn-1, but not Oct-1, strongly enhanced androgen activation. This correlated with Brn-1's preference for the consensus octamer sequence in DNA binding assays. Direct interaction of AR with glutathione-S-transferase-(GST)-fused Oct-1 was DNA-dependent, while Brn-1-AR association was not. Chimeric Brn-1 and Oct-1 POU domains demonstrated that the DNA-dependent AR interaction relied on the origin of the POU homeodomain. However, in the context of full-length Brn-1 and Oct-1 chimeric proteins, the POU homedomain was not sufficient to confer the distinct behaviors of these factors in vivo, but instead revealed the importance of an N-terminal transactivation domain in Brn-1. These results demonstrate that functional interaction of Oct-1 and Brn-1 with AR is determined by the precise sequence of the octamer binding site, and by differential interaction of the POU factors with AR and other components of the transcriptional machinery. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.