Nordeen S K, Suh B J, Kühnel B, Hutchison C A
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262.
Mol Endocrinol. 1990 Dec;4(12):1866-73. doi: 10.1210/mend-4-12-1866.
Analysis of the relative inducibility of an extensive series of mutant glucocorticoid response elements (GREs) defines features critical to the constitution of an active GRE. Assuming that function as a GRE reflects binding of glucocorticoid receptor, our activity data are consistent with the recognition of the GRE as two hexamer half-sites, each half-site recognized by a single subunit of a receptor dimer, probably in a cooperative fashion. Integrity of both half-sites is necessary for an active element, and spacing of the half-sites is critical. The identity of 1 basepair within the hexamer half-site is unconstrained; the receptor probably makes no base-specific contacts at this position. In contrast, at other positions within the half-site, limited substitutions (if any) can be tolerated. These results along with data from certain insertion mutations suggest that the receptor recognizes each hexamer half-site as two separable subelements. A further implication is that the DNA-binding domain of the glucocorticoid receptor is composed of distinct subdomains, which interact with the subelements of the recognition sequence.
对一系列广泛的突变糖皮质激素反应元件（GREs）的相对诱导性分析确定了构成活性GRE的关键特征。假设作为GRE的功能反映了糖皮质激素受体的结合，我们的活性数据与将GRE识别为两个六聚体半位点一致，每个半位点由受体二聚体的单个亚基识别，可能是以协同方式。两个半位点的完整性对于活性元件是必需的，并且半位点的间距至关重要。六聚体半位点内1个碱基对的身份不受限制；受体可能在该位置不进行碱基特异性接触。相比之下，在半位点内的其他位置，可以容忍有限的替代（如果有的话）。这些结果以及来自某些插入突变的数据表明，受体将每个六聚体半位点识别为两个可分离的亚元件。进一步的含义是，糖皮质激素受体的DNA结合结构域由不同的亚结构域组成，这些亚结构域与识别序列的亚元件相互作用。
