Steroid hormone action in eucaryotic cells.
Steroid hormone action in eucaryotic cells.
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类固醇激素在真核细胞中的作用。
DOI：
10.1172/jci111425
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
B. O’Malley
中科院分区：
文献类型：
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作者：
B. O’Malley
图1.真核细胞（例如鸡输卵管）中类固醇激素作用途径的示意图。在该方案中，黄体酮与受体复合物结合，并与间期染色体相互作用，可能位于可调节基因的 5' 侧翼 DNA 处或附近。基因激活发生并有一个很大的前兆——它指导 RNA 聚合酶 II 在位于下游 32 个碱基的正确位点启动转录。如果 TATA 盒内的 GC 只改变了一个碱基对，那么准确的转录就会被取消 (26, 27)。这一结果得到了许多其他实验室对多种基因的类似观察的支持(26)。尽管TATA盒可以被认为是真核启动子区域的一部分，但它最多只能是序列参与者之一，因为它不具有调节基因转录速率的强大能力。事实上，位于 TATA 盒上游稍远的序列（-95 至-48）形成基础启动子的重要部分。然而，“激素控制”区域似乎在结构上是独立的并且位于更上游（-222至-95）。这些区域如图 2 所示，下面将更详细地讨论该假设的实验证据。最后，我们试图确定类固醇受体-DNA 相互作用在卵清蛋白基因表达的激素调节诱导中的重要性。为此，我们寻找可能表现出优先吸引类固醇受体能力的 DNA 序列。事实上，在激素控制区域（-200 到
Figure 1. Schematic representation of the pathway for steroid hormone action in a eucaryotic cell (eg, chicken oviduct). In this scheme, progesterone binds to the receptor complex and it interacts with interphase chromosomes, presumably at or near the 5'-flanking DNA of regulatable genes. Gene activation occurs and a large precur-that it directs RNA polymerase II to initiate transcription at the proper site located 32 bases downstream. If as little as a single base pair is changedto a GC within the TATA box, accurate transcription is abolished (26, 27). Thisresult is sup-ported by similar observations ina number ofother laboratories for a variety of genes (26).Although the TATA box may be considered as a part of the eucaryotic promoter region, it can be no more than one of the sequence participants because it does not have a great capacity to modulate the rate of gene transcription. In fact, sequences located slightly further upstream from the TATA box (-95 to-48) form an important part of the basal promoter. The" hormone control" region, however, appears to be structurally sep-arate andis located further upstream (-222 to-95). These regions are shown schematically in Fig. 2 and the experimental evidence for this hypothesis is discussed in more detail below. Finally, we have attempted to ascertain the importance of steroid receptor-DNA interactions in the hormone-regulatable induction of ovalbumin gene expression. Toward this end, we have searched for DNA sequences that might display a capacity to preferentially attract steroid receptors. In fact, such a region has been identified within this hormone control region (-200 to