Pfahl M, McGinnis D, Hendricks M, Groner B, Hynes N E
Science. 1983 Dec 23;222(4630):1341-3. doi: 10.1126/science.6318311.
Steroid hormones, when complexed to their receptors, recognize and bind specific DNA sequences and subsequently induce increased levels of transcription. The mechanisms of steroid hormone action were analyzed by constructing chimeric DNA molecules from portions of mouse mammary tumor virus envelope and long terminal repeat (LTR) regions ligated to the thymidine kinase (tk) gene of herpes simplex virus. This construction allowed the tk gene to be expressed in a hormone-responsive fashion upon transfection into Ltk- cells. Comparison of transcription data with in vitro binding data showed that hormone-responsive transcription can be directly correlated to the presence of steroid hormone receptor binding sites on the DNA. There are at least two such receptor binding sites in the LTR region, one between -202 and -137 and another between -137 and -50 base pairs from the RNA cap site, as well as a site near the 5' end of the envelope region. These results strengthen the hypothesis that steroid-receptor complexes regulate genes primarily by binding to DNA sites near the promoter region and thereby modulate transcription.
类固醇激素与它们的受体结合后，能够识别并结合特定的DNA序列，随后诱导转录水平升高。通过构建嵌合DNA分子来分析类固醇激素的作用机制，该嵌合DNA分子由小鼠乳腺肿瘤病毒包膜部分和长末端重复序列（LTR）区域与单纯疱疹病毒的胸苷激酶（tk）基因连接而成。这种构建使得tk基因在转染到Ltk-细胞后能够以激素应答的方式表达。转录数据与体外结合数据的比较表明，激素应答性转录可直接与DNA上类固醇激素受体结合位点的存在相关。在LTR区域至少有两个这样的受体结合位点，一个在距RNA帽位点-202至-137之间，另一个在-137至-50碱基对之间，以及包膜区域5'端附近的一个位点。这些结果强化了这样的假设，即类固醇 - 受体复合物主要通过与启动子区域附近的DNA位点结合来调节基因，从而调节转录。
