Green S, Kumar V, Theulaz I, Wahli W, Chambon P
INSERM Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
EMBO J. 1988 Oct;7(10):3037-44. doi: 10.1002/j.1460-2075.1988.tb03168.x.
Steroid hormone receptors activate specific gene transcription by binding as hormone-receptor complexes to short DNA enhancer-like elements termed hormone response elements (HREs). We have shown previously that a highly conserved 66 amino acid region of the oestrogen (ER) and glucocorticoid (GR) receptors, which corresponds to part of the receptor DNA binding domain (region C) is responsible for determining the specificity of target gene activation. This region contains two sub-regions (CI and CII) analogous to the 'zinc-fingers' of the transcription factor TFIIIA. We show here that CI and CII appear to be separate domains both involved in DNA binding. Furthermore, using chimaeric ERs in which either the first (N-terminal) (CI) or second (CII) 'zinc finger' region has been exchanged with that of the GR, indicates that it is the first 'zinc finger' which largely determines target gene specificity. We suggest that receptor recognition of the HRE is analogous to that of the helix-turn-helix DNA binding motif in that the receptor binds to DNA as a dimer with the first 'zinc finger' lying in the major groove recognizing one half of the palindromic HRE, and that protein-DNA interaction is stabilized through non-specific DNA binding and dimer interactions contributed by the second 'zinc finger'.
类固醇激素受体通过作为激素-受体复合物与称为激素反应元件（HREs）的短DNA增强子样元件结合来激活特定基因转录。我们之前已经表明，雌激素（ER）和糖皮质激素（GR）受体的一个高度保守的66个氨基酸区域，对应于受体DNA结合结构域（区域C）的一部分，负责确定靶基因激活的特异性。该区域包含两个类似于转录因子TFIIIA“锌指”的子区域（CI和CII）。我们在此表明，CI和CII似乎是参与DNA结合的独立结构域。此外，使用其中第一个（N端）（CI）或第二个（CII）“锌指”区域已与GR的相应区域交换的嵌合ERs表明，很大程度上是第一个“锌指”决定了靶基因特异性。我们认为，受体对HRE的识别类似于螺旋-转角-螺旋DNA结合基序，即受体作为二聚体与DNA结合，第一个“锌指”位于识别回文HRE一半的大沟中，并且蛋白质-DNA相互作用通过非特异性DNA结合和第二个“锌指”贡献的二聚体相互作用得以稳定。
